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Study No.: 111347 (10PN-PD-DIT-041 EXT:007 Y4)

Title: Assessment of long-term antibody persistence and immunological memory in children previously vaccinated with four pneumococcal conjugate vaccine doses and assessment of pneumococcal catch-up vaccination with GSK1024850A at 5 years of age. GSK1024850A (10Pn-PD-DiT): GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine.

Rationale: The aim of the study was to evaluate the long-term persistence of antibodies against Streptococcus pneumoniae (S. pneumoniae) in children in their 6th year of life previously primed and boosted with the 10Pn-PD-DiT (10Pn group), or with Prevenar® (Prev group), or with Prevenar® and 10Pn-PD-DiT vaccines (Pr-10Pn group) at approximately 48 months (Month 48/Year 4) post booster vaccination. Subjects were primed with the 10Pn-PD-DiT and/or Prevenar® vaccines (Primed Subjects) as part of the primary vaccination 105553 (10PN-PD-DIT-001) study and the booster vaccination 107046 (10PN-PD-DIT-007 BST: 001) study. The persistence in primed subjects was assessed in the persistence studies 111345 (10PN-PD-DIT-041 EXT: 007 Y1) and 111346 (10PN-PD-DIT-041 EXT:007 Y2), and in this 11347 study (10PN-PD-DIT-041 EXT: 007 Y4) These subjects were offered an additional dose of the 10Pn-PD-DiT vaccine at 64-68 months of age as part of this 111347 study, to assess immunological memory 4 years following a 3+1 vaccination course in the first two years of life. In addition, this 111347 study aimed at assessing the immunogenicity and safety of the 10Pn-PD-DiT vaccine following a 2-dose catch-up vaccination in age-matched children in their 6th year of life who had previously not been vaccinated with any pneumococcal vaccine. This study included a persistence analysis in primed subjects, up to 48 months post booster vaccination (Month 48),. Please refer to the 105553, 107046, 111345 and 111346 CTRS for design and results of the primary, booster, persistence Year 1 and Year 2 studies. Prevenar™ (Prev): Pfizer’s 7-valent pneumococcal conjugate vaccine with diphtheria CRM197 as protein carrier.

Phase: III

Study Period: 13 May 2011 to 21 November 2011

Study Design: Open label, controlled, multi-centre, long-term follow-up study with 4 parallel groups.

Centres: 6 centres in Poland

Indication: Vaccination against Streptococcus pneumoniae in healthy subjects who completed the primary vaccination study 10PN-PD-DIT-001 and booster vaccination study 10PN-PD-DIT-007 in Poland and in age-matched unprimed subjects.

Treatment: The study groups were as follows: Primed Subjects: Study groups were based on those in the primary 105553 and booster 107046 studies:

10Pn Group: Subjects aged between 64 and 68 months, previously vaccinated with, respectively, 3 doses and 1 dose of the 10Pn-PD-DiT vaccine as part of the primary 105553 and booster 107406 studies, received a 5th dose of the 10Pn-PD-DiT vaccine at Month 48.

Prev Group: Subjects aged between 64 and 68 months previously vaccinated with, respectively, 3 doses and 1 dose of the Prev vaccine as part of the primary 105553 and booster 107406 studies, received one dose of the 10Pn-PD-DiT vaccine at Month 48.

Pr-10Pn Group: Subjects aged between 64 and 68 months previously vaccinated with, respectively, 3 doses of the 10Pn-PD-DiT vaccine and 1 dose of the Prev vaccine as part of the primary 105553 and booster 107406 studies, received one dose of the 10Pn-PD-DiT vaccine at Month 48.

Unprimed Subjects:

Unprimed Group: Age-matched* subjects aged between 64 and 68 months previously unprimed with any pneumococcal vaccine received 2 doses of the 10Pn-PD-DiT vaccine in their 6th year of life at Months 48 and 50.

The 10Pn-PD-DiT vaccine was administered by intramuscular injection in the right or left deltoid muscle. *Age-matching to Primed Subjects was met by first vaccination of unprimed subjects at 64-68 months of age.

Objectives:

To assess the antibody persistence 1 year post booster (12 to 14 months) following a four-dose vaccination course with a pneumococcal conjugate vaccine*

To assess the antibody persistence 2 years post booster (24 to 26 months) following a four-dose vaccination course with a pneumococcal conjugate vaccine**

To assess the antibody persistence 4 years post booster (48 to 50 months) following a four-dose vaccination course with a pneumococcal conjugate vaccine.

*The results linked to this objective were presented in the CTRS of study 111345. ** The results linked to this objective were presented in the CTRS of study 111346.

Primary Outcome/Efficacy Variable: Immunogenicity (Primed Subjects) At the defined time points* for all subjects:

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.05 µg/mL. *.Time point for the 111347 study: 4 years post booster (48 to 50 months) following a 4-dose vaccination course with a pneumococcal conjugate vaccine (Month 48 Post Booster)

Secondary Outcome/Efficacy Variable(s): Immunogenicity (Primed and Unprimed Subjects) At the defined time points% for all subjects:

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A

Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A

Antibody concentrations against protein D (Anti-PD) Seropositivity status was defined as:

- Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F 8.

- Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations 0.05 µg/mL.

- Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A 8. - Anti-PD antibody concentrations 100 EL.U/mL

%Time points for this 111347 study: - Primed Subjects: At Month 48, and at Month 48 + 7-10 days (7-10 days post vaccination in this 111347 study) - Unprimed Subjects: At Month 48, at Month 48 + 7-10 days (7-10 days post Dose 1 vaccination in this 111347

study), and at Month 51 (3 months post Dose 1 vaccination in this 111347 study).

Safety (during long term follow-up period in Primed Subjects)

Occurrence of serious adverse events (SAEs) related to study procedures throughout the entire study period up to the end of the long-term follow-up for antibody persistence (Month 48).

Safety (for vaccination in the 6th year of life in Primed and Unprimed Subjects)

Occurrence of each solicited adverse event (AE), within 4 days after vaccination: o Local (any, grade 3) AEs. o General (any, grade 3, related) AEs.

Occurrence of unsolicited AEs within 31 days after vaccination.

Occurrence of SAEs after vaccination up to study end (Months 48-51). Statistical Methods: The analyses were performed on the Total Enrolled cohort, the Total Vaccinated cohort, the According-To-Protocol (ATP) cohort for persistence and the ATP cohort for immunogenicity.

The Total Enrolled cohort included all subjects enrolled in the long-term follow-up for antibody persistence.

The Total Vaccinated cohort included all subjects vaccinated in the 6th year of life, including all Primed Subjects with additional vaccine dose administration documented and all Unprimed Subjects with at least one vaccine dose administration documented

The ATP cohort for persistence included all primed subjects enrolled in this study, who did not receive a vaccine or product forbidden in the protocol and for whom assay results concerning antibody persistence outcome measures were available for the antibodies against at least one vaccine antigen component for the blood sample taken at each time point of interest.

The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measures were available. This included vaccinated subjects for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sample taken 7-10 days after vaccination for primed subjects and for any of blood samples taken from unprimed subjects (i.e. before vaccination, 7-10 days post-dose 1 and 1 month post-dose 2).

Immunogencity analysis: The analysis of immunogenicity was performed on the ATP cohort for persistence and the ATP cohort for immunogenicity.

The Persistence Analysis in Primed Subjects, up to 48 months post booster vaccination was performed and the Immunological Memory Analysis in Primed and Unprimed Subjects, from Month 48 to Month 51 (1 month after administration of the second vaccine dose in the study). For both analysis, antibody geometric mean concentrations/titres (GMCs/GMTs) and seropositivity rates were calculated with 95% confidence interval (CI) for each group if applicable, for each pneumococcal serotype and for protein D and at each time point where a blood sample results were available.

Safety analysis: The analysis of safety was performed on the Total Enrolled cohort and the Total Vaccinated cohort. The percentages of subjects reporting each individual solicited local and general AE during the 4-day (Days 0-3) after vaccination were tabulated with exact 95% confidence interval (CI) for each group. The same tabulation was done for grade 3 AEs and for general AEs with causal relationship to vaccination. The proportion of subjects with at least one unsolicited AE classified by the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms within the 31-day (Days 0-30) after vaccination was tabulated for each group. The percentages of subjects with SAEs classified by MedDRA preferred terms and reported during the Persistence and Immunological Memory analyses of this 111347 study were tabulated.

Study Population: Primed Subjects: Male or female child subjects who received the full vaccination course (i.e. 3+1 schedule) with a pneumococcal conjugate vaccine during the primary 105553 and booster 107046 vaccination studies in the first 2 years of life, who attended the Year 1 visit of the 111345 study and the Year 2 visit of the 111346 study, free of obvious health problems as established by medical history and clinical examination priori to study entry. Unprimed Subjects: Male or female child subjects not previously vaccinated with any pneumococcal vaccine, aged 64-68 months at the time of first vaccination, free of obvious health problems as established by medical history and clinical examination prior to study entry. Written informed consent was obtained from the parent or guardian of the subject prior to study entry.

Subjects Enrolled in the Persistence Analysis

Number of subjects 10Pn Group

Prev Group

Pr-10Pn Group

Planned, N 370 31 96

Enrolled, N (Total Enrolled cohort) 316 25 85

Completed 316 (100) 25 (100) 85 (100) Total Number Subjects Withdrawn, n (%) 0 (0.0) 0 (0.0) 0 (0.0)

Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0)

Withdrawn due to Lack of Efficacy n (%) Not Applicable Not Applicable Not Applicable

Withdrawn for other reasons n (%) 0 (0.0) 0 (0.0) 0 (0.0) Demographics 10Pn

Group Prev

Group Pr-10Pn Group

N (Total Enrolled cohort) 316 25 85 Females:Males 167:149 12:13 48:37

Mean Age, months (SD) 67.5 (0.80) 67.3 (0.94) 67.4 (0.84)

White - Caucasian / European heritage, n (%) 312 (98.7) 25 (100) 85 (100)

Subjects Enrolled in the Immunological Memory Analysis

Number of subjects 10Pn Group

Prev Group

Pr-10Pn Group

Unprimed Group

Planned, N 370 31 96 100 Randomised, N (Total Vaccinated cohort) 264 20 65 100

Completed $, n (%) 263 (99.6) 19 (95.0) 64 (98.5) 100 (100)

Total Number Subjects Withdrawn, n (%) 1 (0.4) 1 (5.0) 1 (1.5) 0 (0.0) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Withdrawn due to Lack of Efficacy n (%) Not Applicable Not Applicable Not Applicable Not Applicable

Withdrawn for other reasons n (%) 1 (0.4) 1 (5.0) 1 (1.5) 0 (0.0)

Demographics 10Pn Group

Prev Group

Pr-10Pn Group

Unprimed Group

N (Total Vaccinated cohort) 264 20 65 100

Females:Males 139:125 10:10 35:30 53:47 Mean Age£, months (SD) 67.4 (0.84) 67.1 (0.97) 67.3 (0.89) 65.4 (1.31)

White - Caucasian / European heritage, n (%) 261 (98.9) 20 (100) 65 (100) 98 (98.0)

$Vaccination Analysis completion at 1 month post last vaccine dose (Month 49 for Primed Subjects, and Month 51 for Unprimed Subjects) £Age at the time of the 5th additional dose of 10Pn-PD-DiT vaccine (Primed Subjects) or Dose 1 of 10Pn-PD-DiT vaccine (Unprimed Subjects).

Primary Efficacy Results: Seropositivity rates and GMCs for Anti-1, Anti-4, Anti-5, Anti-6B, Anti-7F, Anti-9V, Anti-14, Anti-18C, Anti-19Fand Anti-23F antibodies (22F-inhibition ELISA) (ATP cohort for persistence)

0.05 g/mL* 0.2 g/mL GMC (g/mL)

95%CI 95% CI 95% CI

Antibody Group Timing N n % LL UL n % LL UL value LL UL

Anti-1 10Pn PRE 262 95 36.3 30.4 42.4 35 13.4 9.5 18.1 0.05 0.04 0.06

PIII(M3) 260 259 99.6 97.9 100 250 96.2 93.0 98.1 1.03 0.93 1.15

Pre-Bo 132 118 89.4 82.8 94.1 37 28.0 20.6 36.5 0.12 0.10 0.14

Post-Bo 136 136 100 97.3 100 135 99.3 96.0 100 1.59 1.37 1.84

Post-Y1 262 252 96.2 93.1 98.2 168 64.1 58.0 69.9 0.29 0.26 0.33

Post-Y2 263 250 95.1 91.7 97.3 129 49.0 42.9 55.3 0.19 0.17 0.22

Post-Y4* 263 238 90.5 86.3 93.8 121 46.0 39.9 52.2 0.20 0.17 0.24

Prev PRE 19 9 47.4 24.4 71.1 3 15.8 3.4 39.6 0.06 0.04 0.09

PIII(M3) 19 4 21.1 6.1 45.6 3 15.8 3.4 39.6 0.04 0.02 0.07

Pre-Bo 16 5 31.3 11.0 58.7 3 18.8 4.0 45.6 0.05 0.03 0.09

Post-Bo 17 8 47.1 23.0 72.2 5 29.4 10.3 56.0 0.10 0.04 0.25

Post-Y1 18 5 27.8 9.7 53.5 3 16.7 3.6 41.4 0.05 0.03 0.09

Post-Y2 18 11 61.1 35.7 82.7 2 11.1 1.4 34.7 0.07 0.04 0.12

Post-Y4* 19 14 73.7 48.8 90.9 8 42.1 20.3 66.5 0.17 0.07 0.43

Pr-10Pn PRE 75 27 36.0 25.2 47.9 7 9.3 3.8 18.3 0.05 0.04 0.06

PIII(M3) 74 13 17.6 9.7 28.2 7 9.5 3.9 18.5 0.04 0.03 0.05

Pre-Bo 37 6 16.2 6.2 32.0 1 2.7 0.1 14.2 0.03 0.03 0.04

Post-Bo 36 35 97.2 85.5 99.9 34 94.4 81.3 99.3 1.06 0.76 1.49

Post-Y1 75 72 96.0 88.8 99.2 47 62.7 50.7 73.6 0.27 0.22 0.34

Post-Y2 75 70 93.3 85.1 97.8 31 41.3 30.1 53.3 0.17 0.14 0.21

Post-Y4* 75 71 94.7 86.9 98.5 36 48.0 36.3 59.8 0.23 0.17 0.32

Anti-4 10Pn PRE 261 92 35.2 29.5 41.4 25 9.6 6.3 13.8 0.05 0.04 0.05

PIII(M3) 264 264 100 98.6 100 258 97.7 95.1 99.2 1.68 1.52 1.87

Pre-Bo 135 128 94.8 89.6 97.9 63 46.7 38.0 55.4 0.19 0.16 0.22

Post-Bo 137 137 100 97.3 100 137 100 97.3 100 4.07 3.56 4.66

Post-Y1 262 259 98.9 96.7 99.8 222 84.7 79.8 88.9 0.52 0.45 0.59

Post-Y2 264 254 96.2 93.1 98.2 153 58.0 51.7 64.0 0.27 0.24 0.31

Post-Y4* 263 238 90.5 86.3 93.8 124 47.1 41.0 53.4 0.19 0.16 0.22

Prev PRE 18 3 16.7 3.6 41.4 0 0.0 0.0 18.5 0.03 0.02 0.04

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 3.09 2.27 4.20

Pre-Bo 13 12 92.3 64.0 99.8 5 38.5 13.9 68.4 0.16 0.10 0.26

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 5.47 4.20 7.12

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 0.57 0.43 0.75

Post-Y2 19 19 100 82.4 100 13 68.4 43.4 87.4 0.30 0.22 0.40

Post-Y4* 19 18 94.7 74.0 99.9 12 63.2 38.4 83.7 0.23 0.12 0.41

Pr-10Pn PRE 73 26 35.6 24.7 47.7 10 13.7 6.8 23.8 0.05 0.04 0.06

PIII(M3) 75 75 100 95.2 100 75 100 95.2 100 3.57 3.05 4.19

Pre-Bo 36 36 100 90.3 100 25 69.4 51.9 83.7 0.30 0.22 0.42

Post-Bo 36 36 100 90.3 100 36 100 90.3 100 6.29 4.95 7.99

Post-Y1 75 75 100 95.2 100 72 96.0 88.8 99.2 1.00 0.81 1.22

Post-Y2 75 75 100 95.2 100 64 85.3 75.3 92.4 0.53 0.43 0.66

Post-Y4* 74 72 97.3 90.6 99.7 53 71.6 59.9 81.5 0.31 0.25 0.38

Anti-5 10Pn PRE 261 133 51.0 44.7 57.2 32 12.3 8.5 16.9 0.06 0.05 0.07

PIII(M3) 263 263 100 98.6 100 260 98.9 96.7 99.8 1.70 1.54 1.89

Pre-Bo 135 134 99.3 95.9 100 87 64.4 55.8 72.5 0.24 0.21 0.28

Post-Bo 136 136 100 97.3 100 136 100 97.3 100 2.38 2.02 2.80

Post-Y1 262 261 99.6 97.9 100 226 86.3 81.5 90.2 0.60 0.53 0.68

Post-Y2 264 260 98.5 96.2 99.6 204 77.3 71.7 82.2 0.41 0.37 0.46

Post-Y4* 263 257 97.7 95.1 99.2 189 71.9 66.0 77.2 0.36 0.31 0.40

Prev PRE 19 8 42.1 20.3 66.5 1 5.3 0.1 26.0 0.05 0.03 0.06

PIII(M3) 19 4 21.1 6.1 45.6 2 10.5 1.3 33.1 0.04 0.02 0.06

Pre-Bo 16 6 37.5 15.2 64.6 1 6.3 0.2 30.2 0.04 0.03 0.07

Post-Bo 18 9 50.0 26.0 74.0 4 22.2 6.4 47.6 0.09 0.04 0.25

Post-Y1 18 12 66.7 41.0 86.7 3 16.7 3.6 41.4 0.08 0.04 0.15

Post-Y2 18 10 55.6 30.8 78.5 4 22.2 6.4 47.6 0.07 0.04 0.13

Post-Y4* 19 19 100 82.4 100 7 36.8 16.3 61.6 0.19 0.10 0.35

Pr-10Pn PRE 74 31 41.9 30.5 53.9 10 13.5 6.7 23.5 0.05 0.04 0.07

PIII(M3) 75 15 20.0 11.6 30.8 3 4.0 0.8 11.2 0.03 0.03 0.04

Pre-Bo 37 11 29.7 15.9 47.0 4 10.8 3.0 25.4 0.04 0.03 0.05

Post-Bo 37 36 97.3 85.8 99.9 32 86.5 71.2 95.5 0.90 0.59 1.36

Post-Y1 74 74 100 95.1 100 60 81.1 70.3 89.3 0.45 0.35 0.58

Post-Y2 75 75 100 95.2 100 54 72.0 60.4 81.8 0.35 0.28 0.44

Post-Y4* 74 73 98.6 92.7 100 54 73.0 61.4 82.6 0.35 0.28 0.43

Anti-6B 10Pn PRE 261 143 54.8 48.5 60.9 44 16.9 12.5 22.0 0.07 0.06 0.09

PIII(M3) 261 242 92.7 88.9 95.6 193 73.9 68.2 79.2 0.43 0.37 0.50

Pre-Bo 127 122 96.1 91.1 98.7 71 55.9 46.8 64.7 0.26 0.21 0.31

Post-Bo 134 132 98.5 94.7 99.8 132 98.5 94.7 99.8 2.13 1.80 2.51

Post-Y1 264 259 98.1 95.6 99.4 202 76.5 70.9 81.5 0.48 0.41 0.57

Post-Y2 264 255 96.6 93.6 98.4 184 69.7 63.8 75.2 0.66 0.54 0.82

Post-Y4* 263 258 98.1 95.6 99.4 232 88.2 83.7 91.8 1.30 1.10 1.55

Prev PRE 19 9 47.4 24.4 71.1 3 15.8 3.4 39.6 0.06 0.04 0.10

PIII(M3) 18 18 100 81.5 100 15 83.3 58.6 96.4 0.80 0.41 1.56

Pre-Bo 15 11 73.3 44.9 92.2 1 6.7 0.2 31.9 0.07 0.05 0.11

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 3.73 2.83 4.90

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 0.92 0.54 1.56

Post-Y2 19 19 100 82.4 100 16 84.2 60.4 96.6 0.77 0.38 1.59

Post-Y4* 19 19 100 82.4 100 17 89.5 66.9 98.7 1.19 0.68 2.07

Pr-10Pn PRE 74 41 55.4 43.4 67.0 13 17.6 9.7 28.2 0.07 0.06 0.09

PIII(M3) 74 71 95.9 88.6 99.2 63 85.1 75.0 92.3 0.69 0.52 0.92

Pre-Bo 36 32 88.9 73.9 96.9 15 41.7 25.5 59.2 0.20 0.12 0.32

Post-Bo 36 36 100 90.3 100 36 100 90.3 100 2.34 1.76 3.12

Post-Y1 75 73 97.3 90.7 99.7 63 84.0 73.7 91.4 0.55 0.41 0.73

Post-Y2 75 74 98.7 92.8 100 59 78.7 67.7 87.3 0.90 0.61 1.32

Post-Y4* 75 74 98.7 92.8 100 66 88.0 78.4 94.4 0.97 0.74 1.27

Anti-7F 10Pn PRE 261 203 77.8 72.2 82.7 113 43.3 37.2 49.5 0.15 0.13 0.17

PIII(M3) 264 264 100 98.6 100 263 99.6 97.9 100 1.80 1.64 1.97

Pre-Bo 131 131 100 97.2 100 116 88.5 81.8 93.4 0.50 0.44 0.57

Post-Bo 135 135 100 97.3 100 135 100 97.3 100 3.57 3.15 4.03

Post-Y1 262 262 100 98.6 100 244 93.1 89.4 95.9 0.69 0.63 0.76

Post-Y2 264 263 99.6 97.9 100 233 88.3 83.7 91.9 0.50 0.45 0.56

Post-Y4* 263 260 98.9 96.7 99.8 211 80.2 74.9 84.9 0.44 0.38 0.52

Prev PRE 18 12 66.7 41.0 86.7 8 44.4 21.5 69.2 0.12 0.06 0.24

PIII(M3) 19 9 47.4 24.4 71.1 3 15.8 3.4 39.6 0.06 0.03 0.12

Pre-Bo 15 4 26.7 7.8 55.1 1 6.7 0.2 31.9 0.04 0.02 0.07

Post-Bo 17 9 52.9 27.8 77.0 5 29.4 10.3 56.0 0.12 0.04 0.35

Post-Y1 19 11 57.9 33.5 79.7 5 26.3 9.1 51.2 0.08 0.04 0.17

Post-Y2 19 15 78.9 54.4 93.9 5 26.3 9.1 51.2 0.13 0.07 0.25

Post-Y4* 19 13 68.4 43.4 87.4 9 47.4 24.4 71.1 0.16 0.08 0.36

Pr-10Pn PRE 75 59 78.7 67.7 87.3 27 36.0 25.2 47.9 0.14 0.11 0.19

PIII(M3) 75 23 30.7 20.5 42.4 7 9.3 3.8 18.3 0.04 0.04 0.06

Pre-Bo 37 5 13.5 4.5 28.8 1 2.7 0.1 14.2 0.03 0.03 0.04

Post-Bo 36 36 100 90.3 100 35 97.2 85.5 99.9 2.26 1.59 3.23

Post-Y1 75 75 100 95.2 100 71 94.7 86.9 98.5 0.84 0.68 1.04

Post-Y2 75 75 100 95.2 100 66 88.0 78.4 94.4 0.62 0.50 0.76

Post-Y4* 75 73 97.3 90.7 99.7 64 85.3 75.3 92.4 0.49 0.37 0.65

Anti-9V 10Pn PRE 260 149 57.3 51.0 63.4 62 23.8 18.8 29.5 0.08 0.07 0.09

PIII(M3) 262 262 100 98.6 100 257 98.1 95.6 99.4 1.49 1.34 1.64

Pre-Bo 135 134 99.3 95.9 100 110 81.5 73.9 87.6 0.49 0.40 0.59

Post-Bo 134 134 100 97.3 100 134 100 97.3 100 3.52 3.04 4.07

Post-Y1 263 263 100 98.6 100 245 93.2 89.4 95.9 0.78 0.68 0.89

Post-Y2 264 259 98.1 95.6 99.4 212 80.3 75.0 84.9 0.64 0.52 0.78

Post-Y4* 263 255 97.0 94.1 98.7 203 77.2 71.6 82.1 1.17 0.92 1.47

Prev PRE 19 14 73.7 48.8 90.9 6 31.6 12.6 56.6 0.13 0.07 0.24

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 2.97 2.24 3.95

Pre-Bo 12 12 100 73.5 100 10 83.3 51.6 97.9 0.53 0.29 0.95

Post-Bo 19 19 100 82.4 100 19 100 82.4 100 6.41 4.25 9.67

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 0.97 0.63 1.49

Post-Y2 19 19 100 82.4 100 16 84.2 60.4 96.6 0.65 0.33 1.31

Post-Y4* 19 19 100 82.4 100 14 73.7 48.8 90.9 1.19 0.43 3.27

Pr-10Pn PRE 74 51 68.9 57.1 79.2 28 37.8 26.8 49.9 0.11 0.08 0.15

PIII(M3) 74 74 100 95.1 100 74 100 95.1 100 3.31 2.86 3.84

Pre-Bo 35 35 100 90.0 100 32 91.4 76.9 98.2 0.61 0.45 0.83

Post-Bo 36 36 100 90.3 100 36 100 90.3 100 2.37 1.92 2.92

Post-Y1 75 75 100 95.2 100 69 92.0 83.4 97.0 0.58 0.47 0.71

Post-Y2 75 75 100 95.2 100 57 76.0 64.7 85.1 0.55 0.39 0.79

Post-Y4* 75 72 96.0 88.8 99.2 57 76.0 64.7 85.1 0.67 0.46 0.99

Anti-14 10Pn PRE 261 256 98.1 95.6 99.4 215 82.4 77.2 86.8 0.67 0.57 0.79

PIII(M3) 262 262 100 98.6 100 261 99.6 97.9 100 3.07 2.78 3.40

Pre-Bo 131 125 95.4 90.3 98.3 103 78.6 70.6 85.3 0.58 0.45 0.75

Post-Bo 134 134 100 97.3 100 133 99.3 95.9 100 5.92 4.95 7.09

Post-Y1 263 262 99.6 97.9 100 252 95.8 92.6 97.9 1.25 1.07 1.45

Post-Y2 264 263 99.6 97.9 100 246 93.2 89.4 95.9 1.67 1.38 2.01

Post-Y4* 263 263 100 98.6 100 255 97.0 94.1 98.7 3.66 3.01 4.45

Prev PRE 18 18 100 81.5 100 14 77.8 52.4 93.6 0.50 0.26 0.95

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 4.86 3.18 7.42

Pre-Bo 13 13 100 75.3 100 12 92.3 64.0 99.8 0.79 0.41 1.52

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 8.55 6.07 12.05

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 1.58 0.99 2.52

Post-Y2 19 19 100 82.4 100 18 94.7 74.0 99.9 1.76 0.85 3.65

Post-Y4* 19 19 100 82.4 100 19 100 82.4 100 2.57 1.22 5.42

Pr-10Pn PRE 74 72 97.3 90.6 99.7 61 82.4 71.8 90.3 0.72 0.53 0.98

PIII(M3) 75 75 100 95.2 100 75 100 95.2 100 4.97 4.01 6.15

Pre-Bo 35 34 97.1 85.1 99.9 32 91.4 76.9 98.2 1.34 0.84 2.15

Post-Bo 36 36 100 90.3 100 36 100 90.3 100 5.29 3.75 7.44

Post-Y1 75 75 100 95.2 100 72 96.0 88.8 99.2 1.45 1.11 1.91

Post-Y2 75 75 100 95.2 100 73 97.3 90.7 99.7 1.70 1.22 2.37

Post-Y4* 75 75 100 95.2 100 73 97.3 90.7 99.7 2.94 2.11 4.12

Anti-18C 10Pn PRE 258 174 67.4 61.4 73.1 88 34.1 28.3 40.2 0.12 0.10 0.14

PIII(M3) 262 262 100 98.6 100 251 95.8 92.6 97.9 1.59 1.40 1.81

Pre-Bo 135 132 97.8 93.6 99.5 87 64.4 55.8 72.5 0.26 0.22 0.30

Post-Bo 136 136 100 97.3 100 136 100 97.3 100 5.50 4.80 6.30

Post-Y1 259 259 100 98.6 100 243 93.8 90.2 96.4 0.86 0.77 0.96

Post-Y2 264 262 99.2 97.3 99.9 213 80.7 75.4 85.3 0.55 0.47 0.65

Post-Y4* 263 256 97.3 94.6 98.9 209 79.5 74.1 84.2 0.70 0.58 0.84

Prev PRE 18 15 83.3 58.6 96.4 6 33.3 13.3 59.0 0.12 0.07 0.22

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 2.60 1.90 3.55

Pre-Bo 18 18 100 81.5 100 11 61.1 35.7 82.7 0.25 0.17 0.36

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 5.50 3.76 8.05

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 0.87 0.64 1.19

Post-Y2 19 19 100 82.4 100 17 89.5 66.9 98.7 0.47 0.32 0.69

Post-Y4* 19 19 100 82.4 100 15 78.9 54.4 93.9 0.87 0.40 1.88

Pr-10Pn PRE 75 51 68.0 56.2 78.3 25 33.3 22.9 45.2 0.11 0.08 0.16

PIII(M3) 75 75 100 95.2 100 75 100 95.2 100 2.99 2.49 3.59

Pre-Bo 36 36 100 90.3 100 25 69.4 51.9 83.7 0.28 0.21 0.36

Post-Bo 37 37 100 90.5 100 37 100 90.5 100 7.04 5.38 9.21

Post-Y1 75 75 100 95.2 100 73 97.3 90.7 99.7 0.88 0.72 1.08

Post-Y2 75 75 100 95.2 100 61 81.3 70.7 89.4 0.54 0.42 0.70

Post-Y4* 74 73 98.6 92.7 100 59 79.7 68.8 88.2 0.63 0.45 0.89

Anti-19F 10Pn PRE 258 227 88.0 83.4 91.7 159 61.6 55.4 67.6 0.29 0.25 0.35

PIII(M3) 263 262 99.6 97.9 100 258 98.1 95.6 99.4 2.38 2.08 2.71

Pre-Bo 136 131 96.3 91.6 98.8 104 76.5 68.4 83.3 0.46 0.36 0.60

Post-Bo 137 137 100 97.3 100 137 100 97.3 100 7.40 6.32 8.67

Post-Y1 262 262 100 98.6 100 256 97.7 95.1 99.2 1.40 1.21 1.60

Post-Y2 264 264 100 98.6 100 241 91.3 87.2 94.4 2.12 1.67 2.70

Post-Y4* 263 260 98.9 96.7 99.8 244 92.8 88.9 95.6 4.17 3.40 5.10

Prev PRE 18 14 77.8 52.4 93.6 11 61.1 35.7 82.7 0.23 0.11 0.51

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 3.82 2.84 5.14

Pre-Bo 18 15 83.3 58.6 96.4 4 22.2 6.4 47.6 0.12 0.07 0.21

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 4.93 3.76 6.47

Post-Y1 18 18 100 81.5 100 17 94.4 72.7 99.9 1.42 0.62 3.27

Post-Y2 19 19 100 82.4 100 15 78.9 54.4 93.9 0.97 0.47 2.00

Post-Y4* 19 19 100 82.4 100 18 94.7 74.0 99.9 4.74 2.24 10.00

Pr-10Pn PRE 75 60 80.0 69.2 88.4 40 53.3 41.4 64.9 0.21 0.15 0.29

PIII(M3) 75 75 100 95.2 100 74 98.7 92.8 100 4.28 3.63 5.05

Pre-Bo 36 34 94.4 81.3 99.3 20 55.6 38.1 72.1 0.34 0.19 0.63

Post-Bo 37 37 100 90.5 100 35 94.6 81.8 99.3 6.04 3.96 9.21

Post-Y1 75 75 100 95.2 100 73 97.3 90.7 99.7 1.51 1.16 1.97

Post-Y2 74 74 100 95.1 100 69 93.2 84.9 97.8 2.19 1.50 3.20

Post-Y4* 75 75 100 95.2 100 75 100 95.2 100 4.05 3.03 5.41

Anti-23F 10Pn PRE 259 161 62.2 56.0 68.1 80 30.9 25.3 36.9 0.10 0.08 0.12

PIII(M3) 263 251 95.4 92.2 97.6 227 86.3 81.6 90.2 0.65 0.56 0.75

Pre-Bo 133 124 93.2 87.5 96.9 74 55.6 46.8 64.2 0.24 0.20 0.30

Post-Bo 135 134 99.3 95.9 100 134 99.3 95.9 100 2.83 2.41 3.31

Post-Y1 262 261 99.6 97.9 100 218 83.2 78.1 87.5 0.58 0.50 0.67

Post-Y2 264 259 98.1 95.6 99.4 194 73.5 67.7 78.7 0.67 0.54 0.84

Post-Y4* 262 254 96.9 94.1 98.7 218 83.2 78.1 87.5 1.57 1.26 1.96

Prev PRE 18 13 72.2 46.5 90.3 6 33.3 13.3 59.0 0.11 0.06 0.20

PIII(M3) 19 19 100 82.4 100 19 100 82.4 100 1.82 1.18 2.81

Pre-Bo 12 11 91.7 61.5 99.8 4 33.3 9.9 65.1 0.11 0.07 0.20

Post-Bo 18 18 100 81.5 100 18 100 81.5 100 6.55 4.35 9.88

Post-Y1 19 19 100 82.4 100 19 100 82.4 100 1.29 0.80 2.09

Post-Y2 19 19 100 82.4 100 18 94.7 74.0 99.9 1.21 0.72 2.03

Post-Y4* 19 19 100 82.4 100 19 100 82.4 100 1.64 1.15 2.34

Pr-10Pn PRE 74 40 54.1 42.1 65.7 13 17.6 9.7 28.2 0.07 0.06 0.10

PIII(M3) 74 74 100 95.1 100 72 97.3 90.6 99.7 1.87 1.46 2.40

Pre-Bo 35 34 97.1 85.1 99.9 24 68.6 50.7 83.1 0.40 0.23 0.70

Post-Bo 36 36 100 90.3 100 35 97.2 85.5 99.9 3.84 2.72 5.40

Post-Y1 75 75 100 95.2 100 70 93.3 85.1 97.8 0.73 0.56 0.94

Post-Y2 75 74 98.7 92.8 100 61 81.3 70.7 89.4 0.66 0.48 0.91

Post-Y4* 75 74 98.7 92.8 100 65 86.7 76.8 93.4 1.12 0.79 1.58

N = number of subjects with available results

n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE= before first dose (primary phase) PIII(M3) = 1 month after dose III (primary phase) Pre-Bo= Pre-booster vaccination blood sample (booster phase) Post-Bo =Post-booster vaccination blood sample (booster phase) Post-Y1 = 12 months after booster dose Post-Y2 = 24 months after booster dose Post-Y4 = 48 months after booster dose * Primary outcome variable

Secondary Outcome Variable(s): Seropositivity rates and GMCs for Anti-6A and Anti-19A antibodies (22F-inhibition ELISA) (ATP cohort for persistence)

Antibody Group Timing N 0.05 g/mL 0.2 g/mL GMC (g/mL)

95% CI 95% CI 95% CI

n % LL UL n % LL UL value LL UL

Anti-6A 10Pn PRE 69 39 56.5 44.0 68.4 15 21.7 12.7 33.3 0.08 0.05 0.10

PIII(M3) 69 42 60.9 48.4 72.4 17 24.6 15.1 36.5 0.08 0.06 0.11

Pre-Bo 131 102 77.9 69.8 84.6 33 25.2 18.0 33.5 0.11 0.09 0.14

Post-Bo 136 133 97.8 93.7 99.5 119 87.5 80.7 92.5 0.79 0.64 0.98

Post-Y1 264 253 95.8 92.7 97.9 130 49.2 43.1 55.4 0.27 0.23 0.32

Post-Y2 264 238 90.2 85.9 93.5 137 51.9 45.7 58.1 0.34 0.27 0.42

Post-Y4 263 256 97.3 94.6 98.9 224 85.2 80.3 89.2 0.92 0.77 1.10

Prev PRE 4 3 75.0 19.4 99.4 1 25.0 0.6 80.6 0.11 0.01 0.99

PIII(M3) 4 4 100 39.8 100 4 100 39.8 100 0.71 0.22 2.24

Pre-Bo 16 11 68.8 41.3 89.0 3 18.8 4.0 45.6 0.08 0.05 0.14

Post-Bo 18 18 100 81.5 100 17 94.4 72.7 99.9 1.80 1.06 3.07

Post-Y1 19 19 100 82.4 100 12 63.2 38.4 83.7 0.43 0.24 0.74

Post-Y2 19 19 100 82.4 100 11 57.9 33.5 79.7 0.41 0.18 0.96

Post-Y4 19 18 94.7 74.0 99.9 14 73.7 48.8 90.9 0.69 0.34 1.38

Pr-10Pn PRE 15 12 80.0 51.9 95.7 5 33.3 11.8 61.6 0.13 0.06 0.27

PIII(M3) 16 12 75.0 47.6 92.7 6 37.5 15.2 64.6 0.14 0.07 0.29

Pre-Bo 37 27 73.0 55.9 86.2 14 37.8 22.5 55.2 0.13 0.08 0.21

Post-Bo 37 36 97.3 85.8 99.9 29 78.4 61.8 90.2 0.80 0.49 1.30

Post-Y1 75 71 94.7 86.9 98.5 44 58.7 46.7 69.9 0.28 0.21 0.38

Post-Y2 75 66 88.0 78.4 94.4 41 54.7 42.7 66.2 0.39 0.25 0.59

Post-Y4 74 72 97.3 90.6 99.7 64 86.5 76.5 93.3 0.75 0.55 1.03

Anti-19A 10Pn PRE 69 56 81.2 69.9 89.6 29 42.0 30.2 54.5 0.13 0.10 0.18

PIII(M3) 69 49 71.0 58.8 81.3 21 30.4 19.9 42.7 0.09 0.07 0.12

Pre-Bo 132 116 87.9 81.1 92.9 41 31.1 23.3 39.7 0.14 0.12 0.17

Post-Bo 130 130 100 97.2 100 112 86.2 79.0 91.6 1.10 0.86 1.41

Post-Y1 264 249 94.3 90.8 96.8 151 57.2 51.0 63.2 0.27 0.23 0.32

Post-Y2 264 226 85.6 80.8 89.6 166 62.9 56.7 68.7 0.35 0.28 0.44

Post-Y4 263 260 98.9 96.7 99.8 238 90.5 86.3 93.8 1.30 1.07 1.59

Prev PRE 4 4 100 39.8 100 3 75.0 19.4 99.4 0.37 0.05 2.99

PIII(M3) 4 4 100 39.8 100 2 50.0 6.8 93.2 0.24 0.05 1.19

Pre-Bo 14 9 64.3 35.1 87.2 1 7.1 0.2 33.9 0.06 0.04 0.10

Post-Bo 17 17 100 80.5 100 14 82.4 56.6 96.2 0.61 0.32 1.18

Post-Y1 19 17 89.5 66.9 98.7 8 42.1 20.3 66.5 0.19 0.10 0.38

Post-Y2 19 14 73.7 48.8 90.9 9 47.4 24.4 71.1 0.18 0.08 0.40

Post-Y4 19 18 94.7 74.0 99.9 17 89.5 66.9 98.7 1.08 0.50 2.33

Pr-10Pn PRE 15 14 93.3 68.1 99.8 5 33.3 11.8 61.6 0.15 0.09 0.24

PIII(M3) 16 14 87.5 61.7 98.4 5 31.3 11.0 58.7 0.11 0.07 0.19

Pre-Bo 36 30 83.3 67.2 93.6 11 30.6 16.3 48.1 0.14 0.09 0.20

Post-Bo 37 37 100 90.5 100 30 81.1 64.8 92.0 0.72 0.45 1.14

Post-Y1 75 70 93.3 85.1 97.8 36 48.0 36.3 59.8 0.25 0.18 0.34

Post-Y2 75 65 86.7 76.8 93.4 42 56.0 44.1 67.5 0.31 0.21 0.45

Post-Y4 75 74 98.7 92.8 100 64 85.3 75.3 92.4 1.14 0.77 1.68

N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE= before first dose (primary phase) PIII(M3) = 1 month after dose III (primary phase) Pre-Bo= Pre-booster vaccination blood sample (booster phase) Post-Bo =Post-booster vaccination blood sample (booster phase) Post-Y1 = 12 months after booster dose Post-Y2 = 24 months after booster dose Post-Y4 = 48 months after booster dose

Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-1, OPSONO-4, OPSONO-5, OPSONO-6B, OPSONO-7F, OPSONO-9V, OPSONO-14, OPSONO-18C, OPSONO-19F and OPSONO-23F titres (ATP cohort for persistence)

Antibody Group Timing N 8 GMT

95% CI 95% CI

n % LL UL value LL UL

OPSONO-1 10Pn PIII(M3) 63 42 66.7 53.7 78.0 24.4 16.7 35.4

Pre-Bo 125 18 14.4 8.8 21.8 6.1 5.0 7.5

Post-Bo 112 105 93.8 87.5 97.5 239.0 174.6 327.2

Post-Y1 239 132 55.2 48.7 61.6 17.1 14.2 20.8

Post-Y2 253 67 26.5 21.2 32.4 8.5 7.2 10.1

Post-Y4 250 55 22.0 17.0 27.7 8.8 7.1 10.9

Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0

Pre-Bo 12 1 8.3 0.2 38.5 5.3 2.9 9.7

Post-Bo 14 0 0.0 0.0 23.2 4.0 4.0 4.0

Post-Y1 16 2 12.5 1.6 38.3 5.5 3.3 9.0

Post-Y2 16 0 0.0 0.0 20.6 4.0 4.0 4.0

Post-Y4 16 1 6.3 0.2 30.2 4.6 3.4 6.4

Pr-10Pn PIII(M3) 14 3 21.4 4.7 50.8 8.4 2.9 24.1

Pre-Bo 35 3 8.6 1.8 23.1 5.6 3.7 8.3

Post-Bo 29 16 55.2 35.7 73.6 16.4 9.5 28.5

Post-Y1 69 24 34.8 23.7 47.2 8.4 6.4 11.0

Post-Y2 71 13 18.3 10.1 29.3 6.4 4.9 8.4

Post-Y4 72 17 23.6 14.4 35.1 8.9 5.9 13.2

OPSONO-4 10Pn PIII(M3) 63 63 100 94.3 100 767.7 595.9 989.1

Pre-Bo 113 47 41.6 32.4 51.2 16.1 11.3 23.0

Post-Bo 114 114 100 96.8 100 2402.7 2036.2 2835.1

Post-Y1 229 139 60.7 54.0 67.1 62.7 45.3 87.0

Post-Y2 240 107 44.6 38.2 51.1 32.5 23.5 45.2

Post-Y4 232 107 46.1 39.6 52.8 37.9 27.2 52.8

Prev PIII(M3) 2 2 100 15.8 100 1041.2 1.1 1031714

Pre-Bo 11 1 9.1 0.2 41.3 7.6 1.8 31.5

Post-Bo 13 13 100 75.3 100 2856.5 1789.8 4558.9

Post-Y1 15 13 86.7 59.5 98.3 225.0 79.1 639.7

Post-Y2 16 7 43.8 19.8 70.1 41.6 9.5 182.2

Post-Y4 16 8 50.0 24.7 75.3 62.2 13.6 284.7

Pr-10Pn PIII(M3) 14 14 100 76.8 100 924.7 514.8 1660.8

Pre-Bo 33 20 60.6 42.1 77.1 63.4 24.6 163.1

Post-Bo 30 30 100 88.4 100 1997.5 1351.2 2953.1

Post-Y1 66 52 78.8 67.0 87.9 93.3 55.5 157.0

Post-Y2 65 38 58.5 45.6 70.6 39.9 22.3 71.5

Post-Y4 63 33 52.4 39.4 65.1 50.7 26.5 97.0

OPSONO-5 10Pn PIII(M3) 61 55 90.2 79.8 96.3 57.9 41.4 81.0

Pre-Bo 117 35 29.9 21.8 39.1 6.9 5.8 8.2

Post-Bo 111 109 98.2 93.6 99.8 151.5 115.6 198.6

Post-Y1 225 167 74.2 68.0 79.8 25.2 21.0 30.2

Post-Y2 251 124 49.4 43.1 55.8 11.9 10.1 13.9

Post-Y4 243 80 32.9 27.0 39.2 7.7 6.8 8.9

Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0

Pre-Bo 11 0 0.0 0.0 28.5 4.0 4.0 4.0

Post-Bo 14 0 0.0 0.0 23.2 4.0 4.0 4.0

Post-Y1 16 2 12.5 1.6 38.3 6.1 3.3 11.3

Post-Y2 16 1 6.3 0.2 30.2 4.2 3.8 4.6

Post-Y4 15 2 13.3 1.7 40.5 5.3 3.5 8.1

Pr-10Pn PIII(M3) 14 2 14.3 1.8 42.8 7.0 2.9 16.8

Pre-Bo 34 0 0.0 0.0 10.3 4.0 4.0 4.0

Post-Bo 30 10 33.3 17.3 52.8 9.8 5.6 17.2

Post-Y1 68 38 55.9 43.3 67.9 12.6 9.4 16.9

Post-Y2 71 23 32.4 21.8 44.5 7.3 5.7 9.4

Post-Y4 68 11 16.2 8.4 27.1 5.5 4.5 6.6

OPSONO-6B 10Pn PIII(M3) 60 56 93.3 83.8 98.2 561.8 378.1 834.6

Pre-Bo 114 56 49.1 39.6 58.7 39.9 24.3 65.3

Post-Bo 113 109 96.5 91.2 99.0 1083.6 827.5 1419.0

Post-Y1 239 112 46.9 40.4 53.4 34.4 24.3 48.8

Post-Y2 245 174 71.0 64.9 76.6 172.3 120.8 245.6

Post-Y4 250 223 89.2 84.7 92.8 875.7 658.7 1164.3

Prev PIII(M3) 2 2 100 15.8 100 1448.2 120.7 17373.8

Pre-Bo 10 3 30.0 6.7 65.2 24.5 2.7 219.0

Post-Bo 13 13 100 75.3 100 4736.3 3127.8 7172.1

Post-Y1 15 14 93.3 68.1 99.8 672.1 178.0 2537.4

Post-Y2 16 14 87.5 61.7 98.4 550.1 180.0 1681.7

Post-Y4 16 15 93.8 69.8 99.8 978.3 395.3 2421.3

Pr-10Pn PIII(M3) 14 12 85.7 57.2 98.2 661.0 172.2 2536.9

Pre-Bo 32 16 50.0 31.9 68.1 33.1 13.7 80.2

Post-Bo 29 27 93.1 77.2 99.2 653.5 337.0 1267.1

Post-Y1 68 32 47.1 34.8 59.6 39.1 19.6 78.1

Post-Y2 68 54 79.4 67.9 88.3 248.1 127.3 483.7

Post-Y4 68 62 91.2 81.8 96.7 716.4 417.4 1229.7

OPSONO-7F 10Pn PIII(M3) 62 62 100 94.2 100 2594.6 1918.8 3508.5

Pre-Bo 112 87 77.7 68.8 85.0 400.3 240.8 665.4

Post-Bo 113 112 99.1 95.2 100 4846.4 3876.0 6059.7

Post-Y1 234 231 98.7 96.3 99.7 1955.4 1681.2 2274.2

Post-Y2 250 250 100 98.5 100 1557.5 1399.6 1733.3

Post-Y4 249 248 99.6 97.8 100 1693.1 1489.3 1924.8

Prev PIII(M3) 2 1 50.0 1.3 98.7 49.4 0.0 3.708E15

Pre-Bo 11 4 36.4 10.9 69.2 40.9 4.5 371.9

Post-Bo 12 5 41.7 15.2 72.3 44.0 6.3 308.5

Post-Y1 15 12 80.0 51.9 95.7 300.2 71.4 1262.5

Post-Y2 16 16 100 79.4 100 1285.8 794.7 2080.3

Post-Y4 15 15 100 78.2 100 965.8 666.8 1398.9

Pr-10Pn PIII(M3) 14 2 14.3 1.8 42.8 11.1 2.5 50.1

Pre-Bo 32 13 40.6 23.7 59.4 45.0 15.3 132.7

Post-Bo 29 28 96.6 82.2 99.9 3120.6 1697.6 5736.5

Post-Y1 67 64 95.5 87.5 99.1 1672.2 1115.8 2506.1

Post-Y2 70 69 98.6 92.3 100 1428.7 1080.1 1889.8

Post-Y4 71 71 100 94.9 100 1602.1 1286.9 1994.5

OPSONO-9V 10Pn PIII(M3) 63 63 100 94.3 100 1272.0 982.3 1647.3

Pre-Bo 117 111 94.9 89.2 98.1 262.6 204.9 336.7

Post-Bo 113 113 100 96.8 100 2776.0 2290.9 3363.7

Post-Y1 234 233 99.6 97.6 100 818.6 704.6 951.0

Post-Y2 249 248 99.6 97.8 100 661.2 568.2 769.4

Post-Y4 250 242 96.8 93.8 98.6 747.4 624.9 894.1

Prev PIII(M3) 2 2 100 15.8 100 1893.2 69.7 51414.9

Pre-Bo 12 11 91.7 61.5 99.8 165.7 63.2 434.5

Post-Bo 12 12 100 73.5 100 4188.9 2236.7 7845.0

Post-Y1 15 15 100 78.2 100 1164.2 585.3 2315.5

Post-Y2 16 16 100 79.4 100 743.7 353.4 1565.0

Post-Y4 15 14 93.3 68.1 99.8 563.8 220.2 1444.0

Pr-10Pn PIII(M3) 14 14 100 76.8 100 1152.1 658.3 2016.2

Pre-Bo 32 31 96.9 83.8 99.9 212.8 137.5 329.3

Post-Bo 30 30 100 88.4 100 969.0 646.1 1453.4

Post-Y1 70 67 95.7 88.0 99.1 391.3 284.3 538.7

Post-Y2 71 68 95.8 88.1 99.1 463.3 318.4 674.2

Post-Y4 70 68 97.1 90.1 99.7 558.6 403.0 774.2

OPSONO-14 10Pn PIII(M3) 63 63 100 94.3 100 1159.6 867.8 1549.5

Pre-Bo 115 91 79.1 70.6 86.1 162.1 109.2 240.6

Post-Bo 118 118 100 96.9 100 2161.8 1802.4 2592.8

Post-Y1 230 228 99.1 96.9 99.9 582.5 506.6 669.8

Post-Y2 242 235 97.1 94.1 98.8 678.0 559.1 822.1

Post-Y4 250 247 98.8 96.5 99.8 1139.8 961.9 1350.5

Prev PIII(M3) 2 2 100 15.8 100 7686.0 76.6 770925.0

Pre-Bo 11 7 63.6 30.8 89.1 84.9 14.7 491.5

Post-Bo 13 13 100 75.3 100 1607.2 852.3 3030.6

Post-Y1 14 14 100 76.8 100 484.5 260.1 902.8

Post-Y2 15 14 93.3 68.1 99.8 387.9 164.6 913.9

Post-Y4 15 14 93.3 68.1 99.8 687.9 267.8 1767.4

Pr-10Pn PIII(M3) 14 14 100 76.8 100 1268.6 558.0 2884.2

Pre-Bo 29 27 93.1 77.2 99.2 357.2 192.6 662.5

Post-Bo 30 30 100 88.4 100 1029.5 742.5 1427.6

Post-Y1 68 67 98.5 92.1 100 475.0 362.6 622.2

Post-Y2 70 67 95.7 88.0 99.1 579.0 403.6 830.5

Post-Y4 71 70 98.6 92.4 100 849.4 645.4 1117.8

OPSONO-18C 10Pn PIII(M3) 63 58 92.1 82.4 97.4 139.4 94.3 206.3

Pre-Bo 118 21 17.8 11.4 25.9 6.8 5.3 8.7

Post-Bo 114 113 99.1 95.2 100 850.2 675.6 1070.0

Post-Y1 218 113 51.8 45.0 58.6 21.0 15.9 27.7

Post-Y2 229 107 46.7 40.1 53.4 29.4 21.3 40.6

Post-Y4 226 121 53.5 46.8 60.2 46.4 33.3 64.5

Prev PIII(M3) 2 2 100 15.8 100 406.6 177.8 930.2

Pre-Bo 12 0 0.0 0.0 26.5 4.0 4.0 4.0

Post-Bo 12 12 100 73.5 100 1237.6 770.1 1989.0

Post-Y1 13 4 30.8 9.1 61.4 12.0 3.5 40.7

Post-Y2 16 7 43.8 19.8 70.1 34.0 8.4 137.8

Post-Y4 16 8 50.0 24.7 75.3 35.3 8.8 142.5

Pr-10Pn PIII(M3) 14 14 100 76.8 100 237.6 123.3 457.9

Pre-Bo 33 5 15.2 5.1 31.9 5.0 4.0 6.2

Post-Bo 30 30 100 88.4 100 678.3 403.3 1140.8

Post-Y1 63 20 31.7 20.6 44.7 11.9 7.4 19.3

Post-Y2 65 25 38.5 26.7 51.4 20.7 11.4 37.6

Post-Y4 63 27 42.9 30.5 56.0 26.6 14.3 49.3

OPSONO-19F 10Pn PIII(M3) 63 58 92.1 82.4 97.4 178.3 109.8 289.7

Pre-Bo 120 49 40.8 32.0 50.2 9.2 7.1 11.8

Post-Bo 110 106 96.4 91.0 99.0 638.7 459.2 888.3

Post-Y1 242 211 87.2 82.3 91.1 55.0 44.4 68.1

Post-Y2 249 201 80.7 75.3 85.4 81.2 60.4 109.2

Post-Y4 247 211 85.4 80.4 89.6 151.7 115.9 198.4

Prev PIII(M3) 2 2 100 15.8 100 90.2 7.3 1119.6

Pre-Bo 11 0 0.0 0.0 28.5 4.0 4.0 4.0

Post-Bo 13 13 100 75.3 100 636.1 323.0 1252.7

Post-Y1 16 13 81.3 54.4 96.0 78.7 24.8 249.6

Post-Y2 16 12 75.0 47.6 92.7 38.1 14.1 102.8

Post-Y4 16 14 87.5 61.7 98.4 178.8 64.6 495.1

Pr-10Pn PIII(M3) 14 13 92.9 66.1 99.8 51.2 20.7 127.0

Pre-Bo 32 5 15.6 5.3 32.8 6.3 4.0 10.1

Post-Bo 30 28 93.3 77.9 99.2 410.3 175.0 961.6

Post-Y1 69 63 91.3 82.0 96.7 61.2 42.8 87.6

Post-Y2 71 61 85.9 75.6 93.0 93.1 56.8 152.7

Post-Y4 69 62 89.9 80.2 95.8 129.3 83.1 201.4

OPSONO-23F 10Pn PIII(M3) 62 59 95.2 86.5 99.0 905.4 608.3 1347.5

Pre-Bo 119 72 60.5 51.1 69.3 84.2 51.0 139.1

Post-Bo 115 115 100 96.8 100 2452.8 1971.4 3051.7

Post-Y1 229 199 86.9 81.8 91.0 609.5 454.4 817.6

Post-Y2 244 202 82.8 77.5 87.3 577.5 418.7 796.7

Post-Y4 239 209 87.4 82.6 91.4 1518.4 1107.9 2080.9

Prev PIII(M3) 2 2 100 15.8 100 5943.3 1.9 18335784

Pre-Bo 11 7 63.6 30.8 89.1 126.8 12.8 1254.0

Post-Bo 12 12 100 73.5 100 24641.6 12642.6 48028.8

Post-Y1 16 16 100 79.4 100 5728.8 2314.2 14182.1

Post-Y2 16 16 100 79.4 100 2820.1 1365.9 5822.8

Post-Y4 15 15 100 78.2 100 3366.1 1599.2 7085.1

Pr-10Pn PIII(M3) 14 14 100 76.8 100 4616.9 2902.1 7344.8

Pre-Bo 31 19 61.3 42.2 78.2 145.5 48.0 441.5

Post-Bo 30 29 96.7 82.8 99.9 2516.2 1364.0 4641.7

Post-Y1 69 63 91.3 82.0 96.7 675.5 433.9 1051.6

Post-Y2 70 57 81.4 70.3 89.7 467.9 254.4 860.6

Post-Y4 65 55 84.6 73.5 92.4 1146.2 596.8 2201.3

N = number of subjects with available results n(%) = number(percentage) of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase) Pre-Bo= Pre-booster vaccination blood sample (booster phase) Post-Bo =Post-booster vaccination blood sample (booster phase) Post-Y1 = 12 months after booster dose Post-Y2 = 24 months after booster dose Post-Y4 = 48 months after booster dose

Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-6A and OPSONO-19A titres (ATP cohort for persistence)

Antibody Group Timing 8 GMT

95% CI 95% CI

N n % LL UL value LL UL

OPSONO-6A 10Pn PIII(M3) 59 36 61.0 47.4 73.5 48.1 27.0 85.7

Pre-Bo 106 46 43.4 33.8 53.4 25.7 16.8 39.2

Post-Bo 110 93 84.5 76.4 90.7 290.7 196.4 430.3

Post-Y1 216 132 61.1 54.3 67.7 59.5 43.7 81.1

Post-Y2 223 170 76.2 70.1 81.7 129.4 96.8 172.8

Post-Y4 231 194 84.0 78.6 88.5 213.5 165.4 275.7

Prev PIII(M3) 2 1 50.0 1.3 98.7 18.1 0.0 3.9052E9

Pre-Bo 11 3 27.3 6.0 61.0 15.9 3.1 83.0

Post-Bo 13 13 100 75.3 100 1516.1 720.6 3189.7

Post-Y1 15 14 93.3 68.1 99.8 655.7 239.9 1792.1

Post-Y2 15 13 86.7 59.5 98.3 283.4 91.6 876.3

Post-Y4 14 12 85.7 57.2 98.2 227.8 72.1 720.0

Pr-10Pn PIII(M3) 14 10 71.4 41.9 91.6 88.3 23.9 326.4

Pre-Bo 26 9 34.6 17.2 55.7 16.1 7.1 36.1

Post-Bo 28 21 75.0 55.1 89.3 104.0 47.4 228.4

Post-Y1 57 38 66.7 52.9 78.6 62.8 35.6 110.9

Post-Y2 65 53 81.5 70.0 90.1 167.3 99.8 280.3

Post-Y4 66 51 77.3 65.3 86.7 153.5 90.5 260.2

OPSONO-19A 10Pn PIII(M3) 57 16 28.1 17.0 41.5 12.4 7.4 21.0

Pre-Bo 125 6 4.8 1.8 10.2 4.9 4.1 5.9

Post-Bo 107 59 55.1 45.2 64.8 31.3 20.3 48.3

Post-Y1 237 34 14.3 10.1 19.5 6.2 5.3 7.3

Post-Y2 251 82 32.7 26.9 38.9 12.6 9.9 16.0

Post-Y4 246 135 54.9 48.4 61.2 31.2 23.6 41.3

Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0

Pre-Bo 13 0 0.0 0.0 24.7 4.0 4.0 4.0

Post-Bo 13 3 23.1 5.0 53.8 13.3 3.3 53.8

Post-Y1 15 2 13.3 1.7 40.5 7.0 3.1 15.8

Post-Y2 16 4 25.0 7.3 52.4 8.8 3.6 21.5

Post-Y4 15 7 46.7 21.3 73.4 14.3 5.6 36.8

Pr-10Pn PIII(M3) 14 1 7.1 0.2 33.9 5.6 2.7 11.7

Pre-Bo 35 0 0.0 0.0 10.0 4.0 4.0 4.0

Post-Bo 29 9 31.0 15.3 50.8 14.1 6.2 32.0

Post-Y1 70 8 11.4 5.1 21.3 5.6 4.4 7.2

Post-Y2 71 19 26.8 16.9 38.6 8.9 6.0 13.1

Post-Y4 68 34 50.0 37.6 62.4 21.8 13.3 35.7

N = number of subjects with available results n(%) = number(percentage) of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase) Pre-Bo= Pre-booster vaccination blood sample (booster phase) Post-Bo =Post-booster vaccination blood sample (booster phase) Post-Y1 = 12 months after booster dose Post-Y2 = 24 months after booster dose Post-Y4 = 48 months after booster dose

Secondary Outcome Variable(s): Seropositivity rates and GMCs for Anti-PD antibodies (ATP cohort for persistence)

Antibody Group Timing N 100 EL.U/mL GMC (EL.U/mL)

95% CI

n % LL UL value LL UL

Anti-PD 10Pn PIII(M3) 261 261 100 98.6 100 1691.3 1519.3 1882.8

Pre-Bo 132 126 95.5 90.4 98.3 633.7 522.9 767.9

Post-Bo 135 134 99.3 95.9 100 3405.4 2888.5 4014.7

Post-Y1 264 253 95.8 92.7 97.9 834.9 724.7 961.9

Post-Y2 264 239 90.5 86.3 93.8 595.1 514.7 688.1

Post-Y4 261 241 92.3 88.4 95.3 372.4 329.6 420.9

Prev PIII(M3) 19 6 31.6 12.6 56.6 85.8 56.0 131.4

Pre-Bo 14 4 28.6 8.4 58.1 113.0 49.7 256.8

Post-Bo 18 6 33.3 13.3 59.0 168.3 61.5 460.1

Post-Y1 19 8 42.1 20.3 66.5 108.0 66.9 174.6

Post-Y2 18 10 55.6 30.8 78.5 131.4 78.5 219.9

Post-Y4 19 12 63.2 38.4 83.7 144.9 86.3 243.2

Pr-10Pn PIII(M3) 73 15 20.5 12.0 31.6 72.7 59.4 88.9

Pre-Bo 34 12 35.3 19.7 53.5 78.7 62.1 99.7

Post-Bo 37 27 73.0 55.9 86.2 166.6 119.6 231.9

Post-Y1 75 52 69.3 57.6 79.5 185.5 145.0 237.3

Post-Y2 75 51 68.0 56.2 78.3 158.4 125.7 199.6

Post-Y4 74 54 73.0 61.4 82.6 161.4 128.4 203.0

N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase) Pre-Bo= Pre-booster vaccination blood sample (booster phase) Post-Bo =Post-booster vaccination blood sample (booster phase) Post-Y1 = 12 months after booster dose Post-Y2 = 24 months after booster dose Post-Y4 = 48 months after booster dose

Secondary Outcome Variable(s): Seropositivity rates and GMCs for Anti-1, Anti-4, Anti-5, Anti-6B, Anti-7F, Anti-9V, Anti-14, Anti-18C, Anti-19F and Anti-23F antibodies (22F-inhibition ELISA) (ATP cohort for immunogenicity)

≥ 0.05 µg/mL ≥ 0.2 µg/mL GMC (µg/mL)

95% CI 95% CI 95% CI

Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-1 10Pn PRE 209 78 37.3 30.7 44.3 31 14.8 10.3 20.4 0.05 0.04 0.06

PIII(M3) 207 206 99.5 97.3 100 199 96.1 92.5 98.3 1.01 0.90 1.13

Pre-Bo 104 92 88.5 80.7 93.9 29 27.9 19.5 37.5 0.12 0.10 0.15 Post-Bo 107 107 100 96.6 100 106 99.1 94.9 100 1.61 1.36 1.91

Post-Y1 209 202 96.7 93.2 98.6 135 64.6 57.7 71.1 0.29 0.25 0.33

Post-Y2 210 199 94.8 90.8 97.4 102 48.6 41.6 55.5 0.19 0.17 0.22

Post-Y4 210 191 91.0 86.2 94.5 94 44.8 37.9 51.8 0.20 0.17 0.25 PI(D7) 208 207 99.5 97.4 100 203 97.6 94.5 99.2 5.36 4.54 6.33

Prev PRE 14 6 42.9 17.7 71.1 2 14.3 1.8 42.8 0.05 0.03 0.09

PIII(M3) 14 3 21.4 4.7 50.8 3 21.4 4.7 50.8 0.04 0.02 0.09 Pre-Bo 12 5 41.7 15.2 72.3 3 25.0 5.5 57.2 0.06 0.03 0.13

Post-Bo 12 7 58.3 27.7 84.8 5 41.7 15.2 72.3 0.15 0.05 0.51

Post-Y1 13 5 38.5 13.9 68.4 3 23.1 5.0 53.8 0.06 0.03 0.14 Post-Y2 13 8 61.5 31.6 86.1 2 15.4 1.9 45.4 0.08 0.04 0.16

Post-Y4 14 10 71.4 41.9 91.6 6 42.9 17.7 71.1 0.19 0.05 0.68

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 3.04 1.22 7.56

Pr-10Pn PRE 55 22 40.0 27.0 54.1 4 7.3 2.0 17.6 0.05 0.04 0.06 PIII(M3) 54 10 18.5 9.3 31.4 6 11.1 4.2 22.6 0.04 0.03 0.05

Pre-Bo 29 4 13.8 3.9 31.7 1 3.4 0.1 17.8 0.03 0.02 0.04

Post-Bo 28 27 96.4 81.7 99.9 26 92.9 76.5 99.1 1.07 0.71 1.60 Post-Y1 55 53 96.4 87.5 99.6 36 65.5 51.4 77.8 0.28 0.22 0.36

Post-Y2 55 52 94.5 84.9 98.9 25 45.5 32.0 59.4 0.18 0.14 0.22

Post-Y4 55 52 94.5 84.9 98.9 29 52.7 38.8 66.3 0.24 0.16 0.37 PI(D7) 54 54 100 93.4 100 54 100 93.4 100 5.00 3.72 6.71

Unprimed PRE 97 69 71.1 61.0 79.9 22 22.7 14.8 32.3 0.10 0.08 0.13

PI(D7) 98 97 99.0 94.4 100 96 98.0 92.8 99.8 1.35 1.08 1.69

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 2.39 2.06 2.78 Anti-4 10Pn PRE 208 69 33.2 26.8 40.0 19 9.1 5.6 13.9 0.04 0.04 0.05

PIII(M3) 211 211 100 98.3 100 206 97.6 94.6 99.2 1.67 1.49 1.88

Pre-Bo 106 102 96.2 90.6 99.0 50 47.2 37.4 57.1 0.19 0.16 0.23 Post-Bo 108 108 100 96.6 100 108 100 96.6 100 4.25 3.67 4.92

Post-Y1 209 207 99.0 96.6 99.9 177 84.7 79.1 89.3 0.51 0.44 0.59

Post-Y2 211 205 97.2 93.9 98.9 123 58.3 51.3 65.0 0.27 0.24 0.31

Post-Y4 210 188 89.5 84.6 93.3 92 43.8 37.0 50.8 0.18 0.15 0.21 PI(D7) 208 208 100 98.2 100 203 97.6 94.5 99.2 12.11 10.08 14.54

Prev PRE 13 2 15.4 1.9 45.4 0 0.0 0.0 24.7 0.03 0.02 0.05

PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 2.85 1.97 4.13 Pre-Bo 8 7 87.5 47.3 99.7 2 25.0 3.2 65.1 0.11 0.06 0.20

Post-Bo 13 13 100 75.3 100 13 100 75.3 100 5.19 3.70 7.27

Post-Y1 14 14 100 76.8 100 14 100 76.8 100 0.54 0.37 0.79 Post-Y2 14 14 100 76.8 100 9 64.3 35.1 87.2 0.29 0.20 0.43

Post-Y4 14 13 92.9 66.1 99.8 7 50.0 23.0 77.0 0.19 0.08 0.43

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 10.45 6.49 16.81

Pr-10Pn PRE 53 22 41.5 28.1 55.9 7 13.2 5.5 25.3 0.05 0.04 0.07 PIII(M3) 55 55 100 93.5 100 55 100 93.5 100 3.62 3.01 4.34

Pre-Bo 28 28 100 87.7 100 18 64.3 44.1 81.4 0.27 0.19 0.39

Post-Bo 28 28 100 87.7 100 28 100 87.7 100 6.12 4.58 8.17 Post-Y1 55 55 100 93.5 100 54 98.2 90.3 100 1.04 0.82 1.32

Post-Y2 55 55 100 93.5 100 48 87.3 75.5 94.7 0.57 0.44 0.75

Post-Y4 54 53 98.1 90.1 100 37 68.5 54.4 80.5 0.32 0.25 0.41 PI(D7) 54 54 100 93.4 100 54 100 93.4 100 7.13 5.18 9.82

Unprimed PRE 97 29 29.9 21.0 40.0 6 6.2 2.3 13.0 0.04 0.03 0.05

PI(D7) 98 98 100 96.3 100 96 98.0 92.8 99.8 4.74 3.77 5.95

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 7.32 6.70 8.00 Anti-5 10Pn PRE 208 109 52.4 45.4 59.4 27 13.0 8.7 18.3 0.06 0.05 0.07

PIII(M3) 211 211 100 98.3 100 209 99.1 96.6 99.9 1.68 1.50 1.89

Pre-Bo 106 105 99.1 94.9 100 68 64.2 54.3 73.2 0.25 0.21 0.29 Post-Bo 107 107 100 96.6 100 107 100 96.6 100 2.47 2.05 2.97

Post-Y1 209 208 99.5 97.4 100 180 86.1 80.7 90.5 0.60 0.52 0.68

Post-Y2 211 207 98.1 95.2 99.5 163 77.3 71.0 82.7 0.41 0.36 0.47

Post-Y4 210 206 98.1 95.2 99.5 153 72.9 66.3 78.7 0.36 0.31 0.41 PI(D7) 208 207 99.5 97.4 100 205 98.6 95.8 99.7 6.23 5.19 7.49

Prev PRE 14 6 42.9 17.7 71.1 1 7.1 0.2 33.9 0.04 0.03 0.07

PIII(M3) 14 3 21.4 4.7 50.8 2 14.3 1.8 42.8 0.04 0.02 0.09 Pre-Bo 12 5 41.7 15.2 72.3 1 8.3 0.2 38.5 0.05 0.03 0.08

Post-Bo 13 6 46.2 19.2 74.9 4 30.8 9.1 61.4 0.12 0.03 0.46

Post-Y1 13 9 69.2 38.6 90.9 3 23.1 5.0 53.8 0.10 0.04 0.22 Post-Y2 13 7 53.8 25.1 80.8 3 23.1 5.0 53.8 0.08 0.04 0.15

Post-Y4 14 14 100 76.8 100 5 35.7 12.8 64.9 0.17 0.08 0.38

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 3.24 1.44 7.29

Pr-10Pn PRE 54 24 44.4 30.9 58.6 8 14.8 6.6 27.1 0.05 0.04 0.07 PIII(M3) 55 12 21.8 11.8 35.0 3 5.5 1.1 15.1 0.04 0.03 0.05

Pre-Bo 29 10 34.5 17.9 54.3 4 13.8 3.9 31.7 0.05 0.03 0.06

Post-Bo 29 28 96.6 82.2 99.9 25 86.2 68.3 96.1 0.90 0.56 1.46 Post-Y1 54 54 100 93.4 100 43 79.6 66.5 89.4 0.47 0.35 0.63

Post-Y2 55 55 100 93.5 100 37 67.3 53.3 79.3 0.34 0.26 0.44

Post-Y4 54 53 98.1 90.1 100 39 72.2 58.4 83.5 0.34 0.26 0.44 PI(D7) 54 54 100 93.4 100 54 100 93.4 100 8.15 5.71 11.63

Unprimed PRE 97 72 74.2 64.3 82.6 24 24.7 16.5 34.5 0.10 0.08 0.12

PI(D7) 98 98 100 96.3 100 90 91.8 84.5 96.4 1.20 0.97 1.49

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 3.10 2.70 3.55 Anti-6B 10Pn PRE 208 113 54.3 47.3 61.2 35 16.8 12.0 22.6 0.07 0.06 0.08

PIII(M3) 208 193 92.8 88.4 95.9 154 74.0 67.5 79.9 0.43 0.36 0.52

Pre-Bo 99 94 94.9 88.6 98.3 56 56.6 46.2 66.5 0.26 0.21 0.34 Post-Bo 105 103 98.1 93.3 99.8 103 98.1 93.3 99.8 2.20 1.81 2.68

Post-Y1 211 207 98.1 95.2 99.5 165 78.2 72.0 83.6 0.48 0.40 0.57

Post-Y2 211 203 96.2 92.7 98.3 144 68.2 61.5 74.5 0.64 0.50 0.81

Post-Y4 210 206 98.1 95.2 99.5 180 85.7 80.2 90.1 1.27 1.04 1.55 PI(D7) 208 207 99.5 97.4 100 206 99.0 96.6 99.9 3.68 3.16 4.29

Prev PRE 14 7 50.0 23.0 77.0 3 21.4 4.7 50.8 0.07 0.03 0.13

PIII(M3) 13 13 100 75.3 100 12 92.3 64.0 99.8 0.88 0.43 1.82 Pre-Bo 10 7 70.0 34.8 93.3 1 10.0 0.3 44.5 0.07 0.04 0.12

Post-Bo 13 13 100 75.3 100 13 100 75.3 100 3.24 2.61 4.04

Post-Y1 14 14 100 76.8 100 14 100 76.8 100 0.69 0.40 1.17

Post-Y2 14 14 100 76.8 100 11 78.6 49.2 95.3 0.65 0.27 1.54

Post-Y4 14 14 100 76.8 100 12 85.7 57.2 98.2 1.20 0.56 2.55 PI(D7) 14 14 100 76.8 100 14 100 76.8 100 2.85 1.89 4.30

Pr-10Pn PRE 54 35 64.8 50.6 77.3 12 22.2 12.0 35.6 0.09 0.06 0.12

PIII(M3) 54 52 96.3 87.3 99.5 45 83.3 70.7 92.1 0.65 0.46 0.92

Pre-Bo 28 25 89.3 71.8 97.7 11 39.3 21.5 59.4 0.16 0.10 0.26 Post-Bo 28 28 100 87.7 100 28 100 87.7 100 2.12 1.54 2.93

Post-Y1 55 53 96.4 87.5 99.6 45 81.8 69.1 90.9 0.53 0.37 0.76

Post-Y2 55 54 98.2 90.3 100 41 74.5 61.0 85.3 0.76 0.48 1.20 Post-Y4 55 54 98.2 90.3 100 50 90.9 80.0 97.0 0.97 0.71 1.33

PI(D7) 54 54 100 93.4 100 53 98.1 90.1 100 2.15 1.62 2.85

Unprimed PRE 97 77 79.4 70.0 86.9 49 50.5 40.2 60.8 0.21 0.15 0.29 PI(D7) 97 94 96.9 91.2 99.4 75 77.3 67.7 85.2 0.53 0.40 0.71

PII(M3) 98 98 100 96.3 100 93 94.9 88.5 98.3 1.25 1.01 1.54

Anti-7F 10Pn PRE 208 162 77.9 71.6 83.3 93 44.7 37.8 51.7 0.15 0.13 0.18

PIII(M3) 211 211 100 98.3 100 210 99.5 97.4 100 1.80 1.62 2.00 Pre-Bo 102 102 100 96.4 100 92 90.2 82.7 95.2 0.52 0.45 0.61

Post-Bo 106 106 100 96.6 100 106 100 96.6 100 3.80 3.30 4.37

Post-Y1 209 209 100 98.3 100 193 92.3 87.9 95.6 0.68 0.61 0.76 Post-Y2 211 211 100 98.3 100 186 88.2 83.0 92.2 0.52 0.46 0.60

Post-Y4 210 208 99.0 96.6 99.9 165 78.6 72.4 83.9 0.43 0.36 0.50

PI(D7) 208 208 100 98.2 100 204 98.1 95.1 99.5 7.16 6.11 8.39

Prev PRE 13 9 69.2 38.6 90.9 5 38.5 13.9 68.4 0.12 0.05 0.28 PIII(M3) 14 7 50.0 23.0 77.0 3 21.4 4.7 50.8 0.08 0.03 0.17

Pre-Bo 10 3 30.0 6.7 65.2 1 10.0 0.3 44.5 0.04 0.02 0.09

Post-Bo 12 8 66.7 34.9 90.1 5 41.7 15.2 72.3 0.20 0.05 0.80 Post-Y1 14 9 64.3 35.1 87.2 4 28.6 8.4 58.1 0.10 0.04 0.25

Post-Y2 14 11 78.6 49.2 95.3 5 35.7 12.8 64.9 0.16 0.07 0.38

Post-Y4 14 10 71.4 41.9 91.6 7 50.0 23.0 77.0 0.17 0.07 0.44 PI(D7) 14 14 100 76.8 100 14 100 76.8 100 3.26 1.67 6.35

Pr-10Pn PRE 55 43 78.2 65.0 88.2 22 40.0 27.0 54.1 0.15 0.10 0.21

PIII(M3) 55 20 36.4 23.8 50.4 6 10.9 4.1 22.2 0.05 0.04 0.07

Pre-Bo 29 4 13.8 3.9 31.7 0 0.0 0.0 11.9 0.03 0.02 0.04 Post-Bo 28 28 100 87.7 100 27 96.4 81.7 99.9 2.01 1.33 3.04

Post-Y1 55 55 100 93.5 100 51 92.7 82.4 98.0 0.83 0.64 1.06

Post-Y2 55 55 100 93.5 100 50 90.9 80.0 97.0 0.64 0.51 0.80 Post-Y4 55 54 98.2 90.3 100 47 85.5 73.3 93.5 0.49 0.36 0.66

PI(D7) 54 54 100 93.4 100 54 100 93.4 100 7.57 5.84 9.81

Unprimed PRE 97 64 66.0 55.7 75.3 36 37.1 27.5 47.5 0.12 0.09 0.16 PI(D7) 98 98 100 96.3 100 93 94.9 88.5 98.3 1.67 1.33 2.09

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 4.55 3.93 5.26

Anti-9V 10Pn PRE 207 117 56.5 49.5 63.4 46 22.2 16.8 28.5 0.07 0.06 0.09

PIII(M3) 209 209 100 98.3 100 206 98.6 95.9 99.7 1.49 1.34 1.66 Pre-Bo 106 105 99.1 94.9 100 87 82.1 73.4 88.8 0.53 0.42 0.66

Post-Bo 105 105 100 96.5 100 105 100 96.5 100 3.71 3.14 4.37

Post-Y1 210 210 100 98.3 100 195 92.9 88.5 95.9 0.77 0.66 0.89 Post-Y2 211 207 98.1 95.2 99.5 172 81.5 75.6 86.5 0.69 0.54 0.87

Post-Y4 210 203 96.7 93.3 98.6 167 79.5 73.4 84.8 1.28 0.98 1.67

PI(D7) 208 208 100 98.2 100 207 99.5 97.4 100 9.94 8.59 11.51

Prev PRE 14 10 71.4 41.9 91.6 4 28.6 8.4 58.1 0.13 0.06 0.30 PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 2.92 2.11 4.04

Pre-Bo 8 8 100 63.1 100 6 75.0 34.9 96.8 0.46 0.22 0.97

Post-Bo 14 14 100 76.8 100 14 100 76.8 100 6.34 3.90 10.29 Post-Y1 14 14 100 76.8 100 14 100 76.8 100 0.94 0.62 1.42

Post-Y2 14 14 100 76.8 100 12 85.7 57.2 98.2 0.53 0.29 0.97

Post-Y4 14 14 100 76.8 100 9 64.3 35.1 87.2 0.86 0.24 3.05

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 9.00 5.49 14.77

Pr-10Pn PRE 54 41 75.9 62.4 86.5 21 38.9 25.9 53.1 0.12 0.09 0.17 PIII(M3) 54 54 100 93.4 100 54 100 93.4 100 3.34 2.80 3.98

Pre-Bo 27 27 100 87.2 100 24 88.9 70.8 97.6 0.61 0.41 0.90

Post-Bo 28 28 100 87.7 100 28 100 87.7 100 2.39 1.88 3.03

Post-Y1 55 55 100 93.5 100 49 89.1 77.8 95.9 0.54 0.42 0.69 Post-Y2 55 55 100 93.5 100 38 69.1 55.2 80.9 0.48 0.31 0.74

Post-Y4 55 52 94.5 84.9 98.9 38 69.1 55.2 80.9 0.54 0.34 0.86

PI(D7) 54 54 100 93.4 100 54 100 93.4 100 5.32 4.08 6.94 Unprimed PRE 97 67 69.1 58.9 78.1 39 40.2 30.4 50.7 0.19 0.12 0.28

PI(D7) 98 94 95.9 89.9 98.9 84 85.7 77.2 92.0 0.90 0.66 1.23

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 2.20 1.85 2.62 Anti-14 10Pn PRE 208 205 98.6 95.8 99.7 173 83.2 77.4 88.0 0.69 0.57 0.82

PIII(M3) 209 209 100 98.3 100 208 99.5 97.4 100 3.03 2.71 3.40

Pre-Bo 103 98 95.1 89.0 98.4 82 79.6 70.5 86.9 0.63 0.47 0.85

Post-Bo 105 105 100 96.5 100 104 99.0 94.8 100 6.10 4.97 7.48 Post-Y1 210 209 99.5 97.4 100 202 96.2 92.6 98.3 1.17 0.99 1.38

Post-Y2 211 210 99.5 97.4 100 196 92.9 88.5 96.0 1.51 1.23 1.86

Post-Y4 210 210 100 98.3 100 203 96.7 93.3 98.6 3.67 2.94 4.57 PI(D7) 208 208 100 98.2 100 208 100 98.2 100 19.38 16.74 22.43

Prev PRE 13 13 100 75.3 100 11 84.6 54.6 98.1 0.54 0.27 1.08

PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 5.05 2.98 8.57

Pre-Bo 9 9 100 66.4 100 8 88.9 51.8 99.7 0.75 0.28 1.99 Post-Bo 13 13 100 75.3 100 13 100 75.3 100 7.76 5.28 11.42

Post-Y1 14 14 100 76.8 100 14 100 76.8 100 1.91 1.09 3.37

Post-Y2 14 14 100 76.8 100 14 100 76.8 100 2.76 1.19 6.44 Post-Y4 14 14 100 76.8 100 14 100 76.8 100 2.16 0.95 4.93

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 13.26 6.91 25.43

Pr-10Pn PRE 54 54 100 93.4 100 47 87.0 75.1 94.6 0.82 0.60 1.12 PIII(M3) 55 55 100 93.5 100 55 100 93.5 100 5.30 4.15 6.78

Pre-Bo 27 26 96.3 81.0 99.9 25 92.6 75.7 99.1 1.24 0.70 2.20

Post-Bo 28 28 100 87.7 100 28 100 87.7 100 5.69 3.78 8.56

Post-Y1 55 55 100 93.5 100 52 94.5 84.9 98.9 1.58 1.13 2.22 Post-Y2 55 55 100 93.5 100 53 96.4 87.5 99.6 1.79 1.18 2.70

Post-Y4 55 55 100 93.5 100 53 96.4 87.5 99.6 3.54 2.35 5.34

PI(D7) 54 54 100 93.4 100 54 100 93.4 100 18.61 14.23 24.34 Unprimed PRE 96 90 93.8 86.9 97.7 55 57.3 46.8 67.3 0.58 0.38 0.87

PI(D7) 98 97 99.0 94.4 100 88 89.8 82.0 95.0 1.72 1.20 2.46

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 7.81 6.34 9.63 Anti-18C 10Pn PRE 205 139 67.8 60.9 74.1 67 32.7 26.3 39.6 0.11 0.09 0.13

PIII(M3) 209 209 100 98.3 100 200 95.7 92.0 98.0 1.62 1.40 1.88

Pre-Bo 106 103 97.2 92.0 99.4 69 65.1 55.2 74.1 0.28 0.23 0.33

Post-Bo 107 107 100 96.6 100 107 100 96.6 100 5.82 4.99 6.78 Post-Y1 206 206 100 98.2 100 192 93.2 88.9 96.2 0.87 0.77 0.99

Post-Y2 211 210 99.5 97.4 100 171 81.0 75.1 86.1 0.55 0.46 0.65

Post-Y4 210 203 96.7 93.3 98.6 162 77.1 70.9 82.6 0.66 0.53 0.82 PI(D7) 208 207 99.5 97.4 100 206 99.0 96.6 99.9 15.51 13.06 18.43

Prev PRE 13 10 76.9 46.2 95.0 4 30.8 9.1 61.4 0.09 0.05 0.17

PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 2.68 1.77 4.08

Pre-Bo 13 13 100 75.3 100 8 61.5 31.6 86.1 0.24 0.14 0.42 Post-Bo 13 13 100 75.3 100 13 100 75.3 100 6.20 3.90 9.87

Post-Y1 14 14 100 76.8 100 14 100 76.8 100 0.85 0.58 1.25

Post-Y2 14 14 100 76.8 100 12 85.7 57.2 98.2 0.44 0.27 0.72 Post-Y4 14 14 100 76.8 100 10 71.4 41.9 91.6 0.53 0.23 1.21

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 19.71 11.87 32.74

Pr-10Pn PRE 55 39 70.9 57.1 82.4 21 38.2 25.4 52.3 0.13 0.09 0.19

PIII(M3) 55 55 100 93.5 100 55 100 93.5 100 3.05 2.47 3.76

Pre-Bo 28 28 100 87.7 100 18 64.3 44.1 81.4 0.24 0.18 0.32 Post-Bo 29 29 100 88.1 100 29 100 88.1 100 6.83 5.04 9.26

Post-Y1 55 55 100 93.5 100 53 96.4 87.5 99.6 0.84 0.65 1.07

Post-Y2 55 55 100 93.5 100 43 78.2 65.0 88.2 0.54 0.39 0.74

Post-Y4 54 53 98.1 90.1 100 42 77.8 64.4 88.0 0.63 0.41 0.96 PI(D7) 54 54 100 93.4 100 54 100 93.4 100 13.34 9.34 19.05

Unprimed PRE 96 52 54.2 43.7 64.4 27 28.1 19.4 38.2 0.10 0.07 0.15

PI(D7) 98 97 99.0 94.4 100 92 93.9 87.1 97.7 2.26 1.66 3.09 PII(M3) 98 98 100 96.3 100 98 100 96.3 100 13.21 11.44 15.25

Anti-19F 10Pn PRE 206 182 88.3 83.2 92.4 126 61.2 54.1 67.9 0.29 0.24 0.36

PIII(M3) 210 209 99.5 97.4 100 206 98.1 95.2 99.5 2.39 2.06 2.78 Pre-Bo 107 104 97.2 92.0 99.4 84 78.5 69.5 85.9 0.49 0.37 0.65

Post-Bo 108 108 100 96.6 100 108 100 96.6 100 7.37 6.14 8.84

Post-Y1 209 209 100 98.3 100 204 97.6 94.5 99.2 1.42 1.22 1.67

Post-Y2 211 211 100 98.3 100 194 91.9 87.4 95.2 1.99 1.53 2.60 Post-Y4 210 208 99.0 96.6 99.9 194 92.4 87.9 95.6 4.04 3.22 5.07

PI(D7) 208 208 100 98.2 100 206 99.0 96.6 99.9 11.63 10.00 13.51

Prev PRE 13 10 76.9 46.2 95.0 9 69.2 38.6 90.9 0.29 0.11 0.78 PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 3.59 2.63 4.89

Pre-Bo 13 11 84.6 54.6 98.1 2 15.4 1.9 45.4 0.10 0.06 0.16

Post-Bo 13 13 100 75.3 100 13 100 75.3 100 4.87 3.55 6.68

Post-Y1 13 13 100 75.3 100 12 92.3 64.0 99.8 1.66 0.54 5.09 Post-Y2 14 14 100 76.8 100 11 78.6 49.2 95.3 1.06 0.42 2.67

Post-Y4 14 14 100 76.8 100 13 92.9 66.1 99.8 3.69 1.38 9.87

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 16.44 10.68 25.29 Pr-10Pn PRE 55 45 81.8 69.1 90.9 30 54.5 40.6 68.0 0.23 0.15 0.34

PIII(M3) 55 55 100 93.5 100 54 98.2 90.3 100 4.27 3.46 5.26

Pre-Bo 28 26 92.9 76.5 99.1 14 50.0 30.6 69.4 0.23 0.13 0.42 Post-Bo 29 29 100 88.1 100 27 93.1 77.2 99.2 5.39 3.22 9.00

Post-Y1 55 55 100 93.5 100 53 96.4 87.5 99.6 1.50 1.08 2.09

Post-Y2 54 54 100 93.4 100 50 92.6 82.1 97.9 2.14 1.33 3.46

Post-Y4 55 55 100 93.5 100 55 100 93.5 100 4.18 2.93 5.96 PI(D7) 54 54 100 93.4 100 54 100 93.4 100 8.09 6.29 10.42

Unprimed PRE 96 75 78.1 68.5 85.9 72 75.0 65.1 83.3 0.60 0.40 0.89

PI(D7) 98 97 99.0 94.4 100 95 96.9 91.3 99.4 5.12 3.97 6.62 PII(M3) 98 98 100 96.3 100 98 100 96.3 100 15.47 13.08 18.29

Anti-23F 10Pn PRE 207 131 63.3 56.3 69.9 63 30.4 24.2 37.2 0.10 0.08 0.12

PIII(M3) 210 200 95.2 91.4 97.7 181 86.2 80.8 90.6 0.64 0.55 0.76 Pre-Bo 104 97 93.3 86.6 97.3 59 56.7 46.7 66.4 0.26 0.20 0.33

Post-Bo 106 105 99.1 94.9 100 105 99.1 94.9 100 2.86 2.38 3.44

Post-Y1 209 208 99.5 97.4 100 174 83.3 77.5 88.0 0.59 0.50 0.70

Post-Y2 211 207 98.1 95.2 99.5 155 73.5 67.0 79.3 0.68 0.53 0.87 Post-Y4 209 202 96.7 93.2 98.6 171 81.8 75.9 86.8 1.44 1.12 1.84

PI(D7) 208 208 100 98.2 100 207 99.5 97.4 100 6.50 5.61 7.53

Prev PRE 13 9 69.2 38.6 90.9 3 23.1 5.0 53.8 0.09 0.05 0.16 PIII(M3) 14 14 100 76.8 100 14 100 76.8 100 1.98 1.17 3.35

Pre-Bo 8 7 87.5 47.3 99.7 3 37.5 8.5 75.5 0.11 0.05 0.25

Post-Bo 13 13 100 75.3 100 13 100 75.3 100 7.15 4.45 11.50

Post-Y1 14 14 100 76.8 100 14 100 76.8 100 1.24 0.78 1.97 Post-Y2 14 14 100 76.8 100 13 92.9 66.1 99.8 1.11 0.64 1.90

Post-Y4 14 14 100 76.8 100 14 100 76.8 100 1.62 1.02 2.57

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 9.34 5.62 15.54 Pr-10Pn PRE 54 30 55.6 41.4 69.1 10 18.5 9.3 31.4 0.08 0.05 0.11

PIII(M3) 54 54 100 93.4 100 54 100 93.4 100 1.93 1.48 2.53

Pre-Bo 27 26 96.3 81.0 99.9 18 66.7 46.0 83.5 0.36 0.19 0.68

Post-Bo 28 28 100 87.7 100 27 96.4 81.7 99.9 3.89 2.57 5.87

Post-Y1 55 55 100 93.5 100 52 94.5 84.9 98.9 0.67 0.50 0.91 Post-Y2 55 54 98.2 90.3 100 44 80.0 67.0 89.6 0.67 0.46 1.00

Post-Y4 55 54 98.2 90.3 100 48 87.3 75.5 94.7 1.09 0.72 1.65

PI(D7) 54 54 100 93.4 100 53 98.1 90.1 100 4.70 3.43 6.45

Unprimed PRE 97 54 55.7 45.2 65.8 30 30.9 21.9 41.1 0.10 0.07 0.14 PI(D7) 98 90 91.8 84.5 96.4 61 62.2 51.9 71.8 0.42 0.30 0.59

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 1.63 1.32 2.01

N = number of subjects with available results n(%) = number(percentage)of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE= prior to first dose of primary phase (for Primed groups)/catch-up vaccination (for Unprimed group) PIII(M3) = 1 month after dose III (primary phase) Pre-Bo = pre-booster vaccination blood sample (booster phase) Post-Bo = post-booster vaccination blood sample (booster phase) Post-Bo (Y1) = 12 months after booster dose Post-Bo (Y2) = 24 months after booster dose Post-Bo (Y4) = 48 months after booster dose PI(D7)= 7 days after additional dose (Primed groups)/ 7 days after dose 1 of the 2-dose catch-up vaccination (Unprimed group) PII(M3)= 1 month after dose 2 of the 2-dose catch-up vaccination

Secondary Outcome Variable(s): Seropositivity rates and GMCs for Anti-6A and Anti-19A antibodies (22F-inhibition ELISA) (ATP cohort for immunogenicity)

≥ 0.05 µg/mL ≥ 0.2 µg/mL GMC (µg/mL)

95% CI 95% CI 95% CI

Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-6A 10Pn PRE 53 32 60.4 46.0 73.5 11 20.8 10.8 34.1 0.07 0.05 0.10

PIII(M3) 52 31 59.6 45.1 73.0 11 21.2 11.1 34.7 0.08 0.06 0.11

Pre-Bo 104 81 77.9 68.7 85.4 28 26.9 18.7 36.5 0.12 0.09 0.15

Post-Bo 107 104 97.2 92.0 99.4 93 86.9 79.0 92.7 0.78 0.62 0.99 Post-Y1 211 203 96.2 92.7 98.3 105 49.8 42.8 56.7 0.27 0.23 0.33

Post-Y2 211 187 88.6 83.5 92.6 103 48.8 41.9 55.8 0.32 0.25 0.42

Post-Y4 210 203 96.7 93.3 98.6 176 83.8 78.1 88.5 0.91 0.74 1.11 PI(D7) 208 208 100 98.2 100 203 97.6 94.5 99.2 2.20 1.85 2.60

Prev PRE 4 3 75.0 19.4 99.4 1 25.0 0.6 80.6 0.11 0.01 0.99

PIII(M3) 4 4 100 39.8 100 4 100 39.8 100 0.71 0.22 2.24 Pre-Bo 12 8 66.7 34.9 90.1 2 16.7 2.1 48.4 0.08 0.04 0.16

Post-Bo 13 13 100 75.3 100 12 92.3 64.0 99.8 1.49 0.78 2.87

Post-Y1 14 14 100 76.8 100 8 57.1 28.9 82.3 0.32 0.20 0.53

Post-Y2 14 14 100 76.8 100 7 50.0 23.0 77.0 0.33 0.12 0.89 Post-Y4 14 13 92.9 66.1 99.8 11 78.6 49.2 95.3 0.73 0.32 1.68

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 1.67 1.00 2.80

Pr-10Pn PRE 12 11 91.7 61.5 99.8 5 41.7 15.2 72.3 0.19 0.09 0.40 PIII(M3) 13 11 84.6 54.6 98.1 6 46.2 19.2 74.9 0.19 0.09 0.43

Pre-Bo 29 21 72.4 52.8 87.3 9 31.0 15.3 50.8 0.12 0.07 0.19

Post-Bo 29 28 96.6 82.2 99.9 23 79.3 60.3 92.0 0.75 0.45 1.26

Post-Y1 55 52 94.5 84.9 98.9 33 60.0 45.9 73.0 0.30 0.20 0.44 Post-Y2 55 47 85.5 73.3 93.5 29 52.7 38.8 66.3 0.33 0.20 0.55

Post-Y4 54 52 96.3 87.3 99.5 47 87.0 75.1 94.6 0.76 0.52 1.11

PI(D7) 54 54 100 93.4 100 51 94.4 84.6 98.8 1.33 0.96 1.83 Unprimed PRE 97 76 78.4 68.8 86.1 50 51.5 41.2 61.8 0.20 0.15 0.27

PI(D7) 98 92 93.9 87.1 97.7 69 70.4 60.3 79.2 0.44 0.33 0.58

PII(M3) 98 97 99.0 94.4 100 91 92.9 85.8 97.1 0.92 0.73 1.16 Anti-19A 10Pn PRE 53 42 79.2 65.9 89.2 21 39.6 26.5 54.0 0.12 0.09 0.17

PIII(M3) 52 39 75.0 61.1 86.0 17 32.7 20.3 47.1 0.10 0.08 0.14

Pre-Bo 104 91 87.5 79.6 93.2 35 33.7 24.7 43.6 0.15 0.12 0.19

Post-Bo 101 101 100 96.4 100 88 87.1 79.0 93.0 1.14 0.87 1.50

Post-Y1 211 199 94.3 90.3 97.0 120 56.9 49.9 63.7 0.28 0.24 0.34

Post-Y2 211 181 85.8 80.3 90.2 131 62.1 55.2 68.7 0.34 0.27 0.43 Post-Y4 210 207 98.6 95.9 99.7 188 89.5 84.6 93.3 1.21 0.97 1.50

PI(D7) 208 208 100 98.2 100 204 98.1 95.1 99.5 2.79 2.33 3.35

Prev PRE 4 4 100 39.8 100 3 75.0 19.4 99.4 0.37 0.05 2.99

PIII(M3) 4 4 100 39.8 100 2 50.0 6.8 93.2 0.24 0.05 1.19 Pre-Bo 10 6 60.0 26.2 87.8 1 10.0 0.3 44.5 0.07 0.03 0.14

Post-Bo 12 12 100 73.5 100 10 83.3 51.6 97.9 0.79 0.33 1.92

Post-Y1 14 13 92.9 66.1 99.8 6 42.9 17.7 71.1 0.24 0.10 0.56 Post-Y2 14 10 71.4 41.9 91.6 6 42.9 17.7 71.1 0.18 0.06 0.50

Post-Y4 14 13 92.9 66.1 99.8 12 85.7 57.2 98.2 0.79 0.30 2.12

PI(D7) 14 14 100 76.8 100 14 100 76.8 100 2.44 1.20 4.96 Pr-10Pn PRE 12 12 100 73.5 100 4 33.3 9.9 65.1 0.17 0.11 0.28

PIII(M3) 13 11 84.6 54.6 98.1 5 38.5 13.9 68.4 0.12 0.07 0.24

Pre-Bo 28 24 85.7 67.3 96.0 8 28.6 13.2 48.7 0.13 0.08 0.19

Post-Bo 29 29 100 88.1 100 23 79.3 60.3 92.0 0.71 0.41 1.22 Post-Y1 55 50 90.9 80.0 97.0 25 45.5 32.0 59.4 0.24 0.16 0.36

Post-Y2 55 47 85.5 73.3 93.5 30 54.5 40.6 68.0 0.29 0.19 0.44

Post-Y4 55 54 98.2 90.3 100 46 83.6 71.2 92.2 1.04 0.65 1.65 PI(D7) 54 54 100 93.4 100 49 90.7 79.7 96.9 1.72 1.14 2.61

Unprimed PRE 97 88 90.7 83.1 95.7 63 64.9 54.6 74.4 0.44 0.32 0.60

PI(D7) 98 97 99.0 94.4 100 87 88.8 80.8 94.3 1.10 0.84 1.45

PII(M3) 98 98 100 96.3 100 98 100 96.3 100 2.39 1.90 3.01

N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE= prior to first dose of primary phase (for Primed groups)/catch-up vaccination (for Unprimed group) PIII(M3) = 1 month after dose III (primary phase) Pre-Bo = pre-booster vaccination blood sample (booster phase) Post-Bo = post-booster vaccination blood sample (booster phase) Post-Bo (Y1) = 12 months after booster dose Post-Bo (Y2) = 24 months after booster dose Post-Bo (Y4) = 48 months after booster dose PI(D7)= 7 days after additional dose (Primed groups)/ 7 days after dose 1 of the 2-dose catch-up vaccination (Unprimed group) PII(M3)= 1 month after dose 2 of the 2-dose catch-up vaccination

Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-1, OPSONO-4, OPSONO-5, OPSONO-6B, OPSONO-7F, OPSONO-9V, OPSONO-14, OPSONO-18C, OPSONO-19F and OPSONO-23F titres (ATP cohort for immunogenicity)

≥ 8 GMT

95% CI 95% CI

Antibody Group Timing N n % LL UL value LL UL

OPSONO-1 10Pn PIII(M3) 47 33 70.2 55.1 82.7 26.2 17.2 40.0 Pre-Bo 97 13 13.4 7.3 21.8 5.9 4.7 7.5

Post-Bo 84 79 94.0 86.7 98.0 233.7 165.8 329.5

Post-Y1 188 104 55.3 47.9 62.6 17.2 13.8 21.3 Post-Y2 207 51 24.6 18.9 31.1 8.1 6.7 9.9

Post-Y4 204 45 22.1 16.6 28.4 8.7 6.9 10.9

PI(D7) 197 193 98.0 94.9 99.4 2920.8 2353.5 3624.7

Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0 Pre-Bo 8 1 12.5 0.3 52.7 6.1 2.3 16.2

Post-Bo 9 0 0.0 0.0 33.6 4.0 4.0 4.0

Post-Y1 11 2 18.2 2.3 51.8 6.3 3.0 13.2 Post-Y2 13 0 0.0 0.0 24.7 4.0 4.0 4.0

Post-Y4 11 0 0.0 0.0 28.5 4.0 4.0 4.0

PI(D7) 13 13 100 75.3 100 1331.0 586.7 3019.5 Pr-10Pn PIII(M3) 11 3 27.3 6.0 61.0 10.3 2.6 40.3

Pre-Bo 27 2 7.4 0.9 24.3 5.1 3.5 7.4

Post-Bo 22 12 54.5 32.2 75.6 15.6 8.6 28.3 Post-Y1 51 17 33.3 20.8 47.9 8.3 6.0 11.4

Post-Y2 52 11 21.2 11.1 34.7 7.0 4.9 9.8

Post-Y4 54 14 25.9 15.0 39.7 9.9 6.0 16.4

PI(D7) 50 48 96.0 86.3 99.5 1816.1 1090.0 3025.8 Unprimed PRE 94 8 8.5 3.7 16.1 5.0 4.2 5.9

PI(D7) 92 90 97.8 92.4 99.7 605.0 462.7 791.2

PII(M3) 95 87 91.6 84.1 96.3 128.3 97.3 169.1 OPSONO-4 10Pn PIII(M3) 47 47 100 92.5 100 805.8 597.0 1087.7

Pre-Bo 89 36 40.4 30.2 51.4 15.7 10.5 23.6

Post-Bo 87 87 100 95.8 100 2569.9 2119.2 3116.4 Post-Y1 179 112 62.6 55.0 69.7 65.7 45.5 94.9

Post-Y2 196 82 41.8 34.8 49.1 28.1 19.6 40.3

Post-Y4 189 86 45.5 38.3 52.9 37.3 25.8 54.1

PI(D7) 196 194 99.0 96.4 99.9 23633.7 19118.5 29215.3 Prev PIII(M3) 2 2 100 15.8 100 1041.2 1.1 1031714

Pre-Bo 7 1 14.3 0.4 57.9 10.9 0.9 127.7

Post-Bo 9 9 100 66.4 100 2673.4 1624.3 4399.9 Post-Y1 10 8 80.0 44.4 97.5 174.2 40.1 757.8

Post-Y2 13 5 38.5 13.9 68.4 28.9 5.9 140.8

Post-Y4 11 5 45.5 16.7 76.6 45.9 6.9 305.4

PI(D7) 13 13 100 75.3 100 10650.3 3969.2 28577.6 Pr-10Pn PIII(M3) 11 11 100 71.5 100 1052.0 504.3 2194.2

Pre-Bo 25 15 60.0 38.7 78.9 60.9 20.4 181.9

Post-Bo 23 23 100 85.2 100 2218.2 1374.7 3579.4 Post-Y1 48 38 79.2 65.0 89.5 100.7 52.8 191.9

Post-Y2 48 31 64.6 49.5 77.8 54.4 27.2 108.8

Post-Y4 45 24 53.3 37.9 68.3 53.0 24.1 116.2 PI(D7) 51 50 98.0 89.6 100 8592.8 5609.3 13163.1

Unprimed PRE 81 17 21.0 12.7 31.5 11.5 7.2 18.3

PI(D7) 93 93 100 96.1 100 18262.1 15571.6 21417.4

PII(M3) 94 94 100 96.2 100 4451.3 3962.4 5000.6 OPSONO-5 10Pn PIII(M3) 45 41 91.1 78.8 97.5 60.4 41.1 88.9

Pre-Bo 96 31 32.3 23.1 42.6 7.2 5.9 8.8

Post-Bo 84 83 98.8 93.5 100 158.4 116.0 216.2 Post-Y1 177 128 72.3 65.1 78.8 24.6 20.0 30.3

Post-Y2 205 99 48.3 41.3 55.4 11.4 9.5 13.5

Post-Y4 196 64 32.7 26.1 39.7 7.7 6.6 9.0 PI(D7) 193 186 96.4 92.7 98.5 822.3 662.7 1020.3

Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0

Pre-Bo 7 0 0.0 0.0 41.0 4.0 4.0 4.0

Post-Bo 9 0 0.0 0.0 33.6 4.0 4.0 4.0 Post-Y1 11 2 18.2 2.3 51.8 7.4 2.9 18.7

Post-Y2 13 1 7.7 0.2 36.0 4.2 3.8 4.7

Post-Y4 10 0 0.0 0.0 30.8 4.0 4.0 4.0 PI(D7) 13 13 100 75.3 100 375.6 217.4 648.9

Pr-10Pn PIII(M3) 11 2 18.2 2.3 51.8 8.2 2.6 25.4

Pre-Bo 27 0 0.0 0.0 12.8 4.0 4.0 4.0

Post-Bo 23 7 30.4 13.2 52.9 9.2 5.1 16.5 Post-Y1 50 30 60.0 45.2 73.6 13.7 9.7 19.4

Post-Y2 52 21 40.4 27.0 54.9 8.0 6.1 10.6

Post-Y4 51 7 13.7 5.7 26.3 5.2 4.2 6.5 PI(D7) 48 47 97.9 88.9 99.9 683.6 428.6 1090.2

Unprimed PRE 92 8 8.7 3.8 16.4 4.9 4.3 5.7

PI(D7) 91 87 95.6 89.1 98.8 295.6 219.4 398.3

PII(M3) 92 89 96.7 90.8 99.3 93.2 73.7 117.8

OPSONO-6B 10Pn PIII(M3) 45 42 93.3 81.7 98.6 571.7 361.2 905.0 Pre-Bo 91 46 50.5 39.9 61.2 39.7 22.9 68.7

Post-Bo 84 81 96.4 89.9 99.3 1092.8 795.6 1500.9

Post-Y1 187 85 45.5 38.2 52.9 30.7 20.8 45.3

Post-Y2 201 146 72.6 65.9 78.7 198.6 134.1 294.1 Post-Y4 203 181 89.2 84.1 93.1 909.7 664.3 1245.7

PI(D7) 198 196 99.0 96.4 99.9 3513.1 2858.1 4318.1

Prev PIII(M3) 2 2 100 15.8 100 1448.2 120.7 17373.8 Pre-Bo 7 2 28.6 3.7 71.0 23.4 1.2 463.6

Post-Bo 9 9 100 66.4 100 4234.4 2538.1 7064.6

Post-Y1 10 9 90.0 55.5 99.7 669.9 119.5 3754.3 Post-Y2 13 11 84.6 54.6 98.1 409.0 106.2 1575.1

Post-Y4 11 10 90.9 58.7 99.8 884.7 242.4 3229.6

PI(D7) 13 13 100 75.3 100 3566.6 2446.1 5200.3

Pr-10Pn PIII(M3) 11 9 81.8 48.2 97.7 618.3 110.3 3466.7 Pre-Bo 26 13 50.0 29.9 70.1 30.2 11.4 80.0

Post-Bo 23 22 95.7 78.1 99.9 678.3 344.8 1334.2

Post-Y1 49 24 49.0 34.4 63.7 45.0 19.3 104.6 Post-Y2 50 40 80.0 66.3 90.0 232.6 104.1 519.9

Post-Y4 51 48 94.1 83.8 98.8 712.0 401.4 1263.0

PI(D7) 50 48 96.0 86.3 99.5 1590.5 942.8 2683.3

Unprimed PRE 79 35 44.3 33.1 55.9 70.7 33.5 149.2 PI(D7) 93 84 90.3 82.4 95.5 1971.4 1238.0 3139.2

PII(M3) 95 94 98.9 94.3 100 2536.9 2014.1 3195.5

OPSONO-7F 10Pn PIII(M3) 46 46 100 92.3 100 2827.4 2011.4 3974.4 Pre-Bo 87 69 79.3 69.3 87.3 423.9 243.4 738.3

Post-Bo 86 85 98.8 93.7 100 5119.2 3893.6 6730.6

Post-Y1 182 181 99.5 97.0 100 2072.2 1777.7 2415.6 Post-Y2 203 203 100 98.2 100 1583.4 1397.7 1793.7

Post-Y4 203 202 99.5 97.3 100 1676.4 1454.6 1932.0

PI(D7) 199 199 100 98.2 100 25196.4 21149.5 30017.6

Prev PIII(M3) 2 1 50.0 1.3 98.7 49.4 0.0 3.708E15 Pre-Bo 7 1 14.3 0.4 57.9 12.4 0.8 199.5

Post-Bo 8 2 25.0 3.2 65.1 20.5 1.5 282.1

Post-Y1 10 8 80.0 44.4 97.5 267.0 37.5 1899.2 Post-Y2 13 13 100 75.3 100 1149.6 665.4 1985.9

Post-Y4 11 11 100 71.5 100 1017.0 616.6 1677.4

PI(D7) 13 13 100 75.3 100 17828.8 10270.4 30949.7 Pr-10Pn PIII(M3) 11 2 18.2 2.3 51.8 14.7 2.1 103.4

Pre-Bo 25 11 44.0 24.4 65.1 55.5 15.7 195.9

Post-Bo 22 21 95.5 77.2 99.9 2920.4 1344.7 6342.4

Post-Y1 47 45 95.7 85.5 99.5 1642.3 1020.2 2644.0 Post-Y2 51 50 98.0 89.6 100 1407.4 991.2 1998.3

Post-Y4 53 53 100 93.3 100 1503.1 1152.4 1960.5

PI(D7) 50 50 100 92.9 100 13098.6 9715.5 17659.8 Unprimed PRE 74 67 90.5 81.5 96.1 1362.8 849.6 2185.8

PI(D7) 93 93 100 96.1 100 19243.4 15701.4 23584.5

PII(M3) 93 93 100 96.1 100 9692.0 8299.3 11318.4

OPSONO-9V 10Pn PIII(M3) 47 47 100 92.5 100 1306.0 950.2 1794.9 Pre-Bo 93 89 95.7 89.4 98.8 271.9 206.5 358.1

Post-Bo 85 85 100 95.8 100 2890.9 2358.8 3543.1

Post-Y1 183 182 99.5 97.0 100 778.1 653.2 926.9 Post-Y2 205 204 99.5 97.3 100 655.4 551.1 779.3

Post-Y4 203 198 97.5 94.3 99.2 806.3 665.5 976.9

PI(D7) 201 201 100 98.2 100 9419.4 7586.0 11695.9

Prev PIII(M3) 2 2 100 15.8 100 1893.2 69.7 51414.9

Pre-Bo 8 8 100 63.1 100 179.4 77.3 416.4 Post-Bo 8 8 100 63.1 100 3252.7 1425.8 7420.6

Post-Y1 10 10 100 69.2 100 1047.1 423.7 2587.5

Post-Y2 13 13 100 75.3 100 784.0 313.1 1963.2

Post-Y4 11 10 90.9 58.7 99.8 443.6 121.3 1621.7 PI(D7) 13 13 100 75.3 100 12234.7 8280.5 18077.3

Pr-10Pn PIII(M3) 11 11 100 71.5 100 1222.3 589.1 2536.4

Pre-Bo 25 24 96.0 79.6 99.9 203.7 124.9 332.2 Post-Bo 23 23 100 85.2 100 972.3 610.6 1548.4

Post-Y1 50 48 96.0 86.3 99.5 381.2 258.6 562.0

Post-Y2 52 50 96.2 86.8 99.5 486.2 310.5 761.2 Post-Y4 52 50 96.2 86.8 99.5 459.7 307.8 686.5

PI(D7) 51 51 100 93.0 100 7730.3 5361.8 11145.2

Unprimed PRE 87 75 86.2 77.1 92.7 398.2 253.8 624.9

PI(D7) 93 93 100 96.1 100 8322.7 6605.7 10486.1 PII(M3) 94 94 100 96.2 100 6456.1 5458.1 7636.6

OPSONO-14 10Pn PIII(M3) 47 47 100 92.5 100 1265.0 898.0 1782.0

Pre-Bo 89 73 82.0 72.5 89.4 187.9 121.3 291.1 Post-Bo 89 89 100 95.9 100 2212.9 1787.5 2739.4

Post-Y1 178 177 99.4 96.9 100 607.4 520.7 708.5

Post-Y2 196 189 96.4 92.8 98.6 646.2 517.6 806.7

Post-Y4 203 201 99.0 96.5 99.9 1207.7 999.2 1459.7 PI(D7) 197 197 100 98.1 100 8572.3 7145.4 10284.3

Prev PIII(M3) 2 2 100 15.8 100 7686.0 76.6 770925.0

Pre-Bo 7 5 71.4 29.0 96.3 157.7 12.4 2004.4 Post-Bo 9 9 100 66.4 100 1639.2 701.7 3828.9

Post-Y1 10 10 100 69.2 100 525.1 246.1 1120.3

Post-Y2 12 11 91.7 61.5 99.8 400.5 137.5 1166.7 Post-Y4 10 9 90.0 55.5 99.7 507.2 137.0 1878.1

PI(D7) 13 13 100 75.3 100 4192.8 2218.6 7923.7

Pr-10Pn PIII(M3) 11 11 100 71.5 100 1250.7 431.3 3626.9

Pre-Bo 24 22 91.7 73.0 99.0 342.9 162.1 725.3 Post-Bo 23 23 100 85.2 100 1228.2 850.7 1773.2

Post-Y1 51 50 98.0 89.6 100 526.3 376.4 735.8

Post-Y2 51 48 94.1 83.8 98.8 617.6 392.2 972.3 Post-Y4 54 53 98.1 90.1 100 955.9 682.8 1338.4

PI(D7) 51 51 100 93.0 100 6883.1 5057.3 9368.0

Unprimed PRE 83 81 97.6 91.6 99.7 586.5 439.0 783.6 PI(D7) 94 94 100 96.2 100 4678.2 3788.0 5777.5

PII(M3) 95 95 100 96.2 100 4891.1 4178.8 5724.8

OPSONO-18C 10Pn PIII(M3) 47 43 91.5 79.6 97.6 152.0 94.2 245.3

Pre-Bo 93 20 21.5 13.7 31.2 7.6 5.7 10.3 Post-Bo 85 84 98.8 93.6 100 875.8 660.4 1161.5

Post-Y1 171 91 53.2 45.4 60.9 21.4 15.7 29.2

Post-Y2 189 87 46.0 38.8 53.4 28.4 20.0 40.4 Post-Y4 183 97 53.0 45.5 60.4 49.6 34.1 72.0

PI(D7) 194 190 97.9 94.8 99.4 3378.9 2652.2 4304.8

Prev PIII(M3) 2 2 100 15.8 100 406.6 177.8 930.2

Pre-Bo 8 0 0.0 0.0 36.9 4.0 4.0 4.0 Post-Bo 8 8 100 63.1 100 1116.5 652.4 1910.7

Post-Y1 8 2 25.0 3.2 65.1 7.4 2.7 20.6

Post-Y2 13 7 53.8 25.1 80.8 55.8 11.0 282.3 Post-Y4 11 4 36.4 10.9 69.2 16.2 3.2 82.5

PI(D7) 13 13 100 75.3 100 3478.6 1788.5 6765.8

Pr-10Pn PIII(M3) 11 11 100 71.5 100 258.2 112.1 594.7

Pre-Bo 27 3 11.1 2.4 29.2 4.4 3.9 4.9

Post-Bo 23 23 100 85.2 100 634.2 340.2 1182.0 Post-Y1 46 13 28.3 16.0 43.5 10.6 6.1 18.2

Post-Y2 46 19 41.3 27.0 56.8 20.2 10.3 39.8

Post-Y4 46 21 45.7 30.9 61.0 31.3 14.8 66.1

PI(D7) 50 48 96.0 86.3 99.5 1663.2 970.5 2850.2 Unprimed PRE 89 7 7.9 3.2 15.5 5.3 4.2 6.6

PI(D7) 92 88 95.7 89.2 98.8 2503.1 1692.6 3701.6

PII(M3) 92 92 100 96.1 100 2255.9 1876.9 2711.4 OPSONO-19F 10Pn PIII(M3) 47 45 95.7 85.5 99.5 199.2 115.4 344.1

Pre-Bo 93 40 43.0 32.8 53.7 9.4 7.0 12.7

Post-Bo 82 79 96.3 89.7 99.2 639.0 430.7 948.0 Post-Y1 191 168 88.0 82.5 92.2 57.5 44.9 73.6

Post-Y2 204 163 79.9 73.7 85.2 76.3 55.0 105.8

Post-Y4 200 170 85.0 79.3 89.6 141.2 104.4 190.9

PI(D7) 196 194 99.0 96.4 99.9 1346.4 1068.6 1696.5 Prev PIII(M3) 2 2 100 15.8 100 90.2 7.3 1119.6

Pre-Bo 7 0 0.0 0.0 41.0 4.0 4.0 4.0

Post-Bo 9 9 100 66.4 100 986.7 609.5 1597.2 Post-Y1 11 9 81.8 48.2 97.7 125.5 28.6 550.6

Post-Y2 13 10 76.9 46.2 95.0 49.7 15.4 160.6

Post-Y4 11 9 81.8 48.2 97.7 104.9 29.1 378.1

PI(D7) 13 13 100 75.3 100 2340.4 654.8 8365.2 Pr-10Pn PIII(M3) 11 10 90.9 58.7 99.8 63.0 20.1 197.3

Pre-Bo 27 4 14.8 4.2 33.7 6.6 3.8 11.5

Post-Bo 23 21 91.3 72.0 98.9 462.1 168.2 1269.4 Post-Y1 51 46 90.2 78.6 96.7 61.2 39.2 95.5

Post-Y2 52 43 82.7 69.7 91.8 93.3 50.2 173.2

Post-Y4 51 45 88.2 76.1 95.6 132.2 77.0 226.9 PI(D7) 50 50 100 92.9 100 662.3 430.0 1020.1

Unprimed PRE 92 30 32.6 23.2 43.2 12.0 8.3 17.5

PI(D7) 93 91 97.8 92.4 99.7 700.2 456.1 1074.9

PII(M3) 93 93 100 96.1 100 1437.7 1146.9 1802.3 OPSONO-23F 10Pn PIII(M3) 46 44 95.7 85.2 99.5 993.5 623.8 1582.3

Pre-Bo 94 61 64.9 54.4 74.5 100.8 57.9 175.5

Post-Bo 88 88 100 95.9 100 2394.5 1856.4 3088.7 Post-Y1 183 160 87.4 81.7 91.9 654.7 471.0 910.0

Post-Y2 198 165 83.3 77.4 88.2 637.2 446.2 909.9

Post-Y4 194 170 87.6 82.2 91.9 1477.4 1046.2 2086.2 PI(D7) 199 197 99.0 96.4 99.9 8700.4 7021.7 10780.5

Prev PIII(M3) 2 2 100 15.8 100 5943.3 1.9 18335784

Pre-Bo 7 5 71.4 29.0 96.3 116.2 5.7 2385.4

Post-Bo 8 8 100 63.1 100 22251.0 8409.9 58871.6 Post-Y1 11 11 100 71.5 100 3969.9 1507.9 10451.5

Post-Y2 13 13 100 75.3 100 2355.4 1011.9 5482.7

Post-Y4 11 11 100 71.5 100 2931.0 1094.8 7847.3 PI(D7) 13 13 100 75.3 100 11341.1 5374.6 23931.0

Pr-10Pn PIII(M3) 11 11 100 71.5 100 5278.2 3041.9 9158.8

Pre-Bo 24 16 66.7 44.7 84.4 189.6 55.1 652.7

Post-Bo 23 22 95.7 78.1 99.9 2634.8 1243.4 5583.4 Post-Y1 49 45 91.8 80.4 97.7 769.3 462.1 1280.7

Post-Y2 52 42 80.8 67.5 90.4 472.4 230.7 967.5

Post-Y4 48 41 85.4 72.2 93.9 1314.1 612.5 2819.7 PI(D7) 50 49 98.0 89.4 99.9 7871.9 4965.3 12480.1

Unprimed PRE 83 47 56.6 45.3 67.5 176.4 83.4 373.2

PI(D7) 96 95 99.0 94.3 100 6813.9 5249.5 8844.6

PII(M3) 95 95 100 96.2 100 5586.1 4666.1 6687.5

N = number of subjects with available results n(%) = number(percentage) of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase) Pre-Bo = pre-booster vaccination blood sample (booster phase) Post-Bo = post-booster vaccination blood sample (booster phase) Post-Bo (Y1) = 12 months after booster dose Post-Bo (Y2) = 24 months after booster dose Post-Bo (Y4) = 48 months after booster dose PRE= prior to catch-up vaccination PI(D7)= 7 days after additional dose (Primed groups)/ 7 days after dose 1 of the 2-dose catch-up vaccination (Unprimed group) PII(M3)= 1 month after dose 2 of the 2-dose catch-up vaccination

Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-6A and OPSONO-19A titres (ATP cohort for immunogenicity)

≥ 8 GMT

95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL

OPSONO-6A 10Pn PIII(M3) 45 28 62.2 46.5 76.2 49.2 25.3 95.5

Pre-Bo 81 35 43.2 32.2 54.7 26.4 16.1 43.2 Post-Bo 84 71 84.5 75.0 91.5 294.9 188.4 461.5

Post-Y1 173 105 60.7 53.0 68.0 60.3 42.5 85.4

Post-Y2 183 144 78.7 72.0 84.4 144.9 106.1 198.1

Post-Y4 192 162 84.4 78.5 89.2 211.2 160.2 278.5 PI(D7) 189 185 97.9 94.7 99.4 1217.7 957.8 1548.2

Prev PIII(M3) 2 1 50.0 1.3 98.7 18.1 0.0 3.9052E9

Pre-Bo 8 1 12.5 0.3 52.7 9.2 1.3 66.3 Post-Bo 9 9 100 66.4 100 916.4 401.4 2092.2

Post-Y1 10 9 90.0 55.5 99.7 336.0 91.8 1229.7

Post-Y2 12 10 83.3 51.6 97.9 193.6 51.0 735.1 Post-Y4 10 8 80.0 44.4 97.5 195.2 39.8 958.0

PI(D7) 12 12 100 73.5 100 1490.2 681.6 3257.8

Pr-10Pn PIII(M3) 11 9 81.8 48.2 97.7 127.1 32.5 497.9

Pre-Bo 20 7 35.0 15.4 59.2 15.7 6.3 39.3 Post-Bo 21 16 76.2 52.8 91.8 105.7 42.9 260.4

Post-Y1 40 27 67.5 50.9 81.4 65.7 32.5 132.8

Post-Y2 49 39 79.6 65.7 89.8 139.4 76.6 253.4 Post-Y4 50 37 74.0 59.7 85.4 130.1 69.5 243.6

PI(D7) 49 46 93.9 83.1 98.7 467.7 293.8 744.5

Unprimed PRE 82 57 69.5 58.4 79.2 102.6 61.5 171.2 PI(D7) 92 88 95.7 89.2 98.8 826.5 593.9 1150.2

PII(M3) 91 87 95.6 89.1 98.8 943.4 691.3 1287.4

OPSONO-19A 10Pn PIII(M3) 42 14 33.3 19.6 49.5 15.8 8.1 30.7

Pre-Bo 97 5 5.2 1.7 11.6 5.2 4.1 6.5 Post-Bo 80 44 55.0 43.5 66.2 30.7 18.4 51.2

Post-Y1 186 30 16.1 11.2 22.2 6.5 5.4 7.9

Post-Y2 206 69 33.5 27.1 40.4 12.6 9.7 16.5 Post-Y4 201 112 55.7 48.6 62.7 31.5 23.2 42.9

PI(D7) 194 173 89.2 83.9 93.2 467.0 335.0 651.1 Prev PIII(M3) 2 0 0.0 0.0 84.2 4.0 4.0 4.0

Pre-Bo 9 0 0.0 0.0 33.6 4.0 4.0 4.0

Post-Bo 9 2 22.2 2.8 60.0 11.1 2.3 52.7 Post-Y1 11 2 18.2 2.3 51.8 8.6 2.7 26.7

Post-Y2 13 3 23.1 5.0 53.8 9.6 3.2 29.1

Post-Y4 11 4 36.4 10.9 69.2 7.3 4.0 13.1

PI(D7) 13 11 84.6 54.6 98.1 437.6 81.3 2356.3 Pr-10Pn PIII(M3) 11 1 9.1 0.2 41.3 6.2 2.3 16.2

Pre-Bo 27 0 0.0 0.0 12.8 4.0 4.0 4.0

Post-Bo 22 7 31.8 13.9 54.9 13.7 5.3 35.6

Post-Y1 50 7 14.0 5.8 26.7 6.0 4.3 8.3 Post-Y2 52 15 28.8 17.1 43.1 9.3 6.0 14.5

Post-Y4 50 25 50.0 35.5 64.5 19.6 11.2 34.3

PI(D7) 48 36 75.0 60.4 86.4 106.1 54.1 208.3 Unprimed PRE 92 25 27.2 18.4 37.4 9.9 7.0 13.8

PI(D7) 90 81 90.0 81.9 95.3 431.2 269.4 689.9

PII(M3) 91 87 95.6 89.1 98.8 376.4 256.3 552.6

N = number of subjects with available results n(% )= number(percentage) of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase) Pre-Bo = pre-booster vaccination blood sample (booster phase) Post-Bo = post-booster vaccination blood sample (booster phase) Post-Bo (Y1) = 12 months after booster dose Post-Bo (Y2) = 24 months after booster dose Post-Bo (Y4) = 48 months after booster dose PRE= prior to catch-up vaccination PI(D7)= 7 days after additional dose (Primed groups)/ 7 days after dose 1 of the 2-dose catch-up vaccination (Unprimed group) PII(M3)= 1 month after dose 2 of the 2-dose catch-up vaccination

Secondary Outcome Variable(s): Seropositivity rates and GMCs for Anti-PD antibodies (ATP cohort for immunogenicity) ≥ 100 EL.U/mL GMC(EL.U/mL)

95% CI 95% CI

Antibody Group Timing N n % LL UL value LL UL

Anti-PD 10Pn PIII(M3) 209 209 100 98.3 100 1641.3 1457.7 1848.1 Pre-Bo 103 101 98.1 93.2 99.8 658.9 535.7 810.5

Post-Bo 106 106 100 96.6 100 3629.0 3078.1 4278.5

Post-Y1 211 203 96.2 92.7 98.3 861.7 736.5 1008.2 Post-Y2 211 190 90.0 85.2 93.7 597.3 507.5 703.0

Post-Y4 208 190 91.3 86.7 94.8 374.3 324.8 431.3

PI(D7) 208 207 99.5 97.4 100 2106.0 1806.7 2454.9

Prev PIII(M3) 14 3 21.4 4.7 50.8 78.5 45.8 134.4 Pre-Bo 10 4 40.0 12.2 73.8 156.5 50.4 485.9

Post-Bo 13 6 46.2 19.2 74.9 268.3 70.0 1028.8

Post-Y1 14 8 57.1 28.9 82.3 142.2 78.4 257.9 Post-Y2 13 8 61.5 31.6 86.1 166.0 85.0 324.3

Post-Y4 14 9 64.3 35.1 87.2 133.3 78.3 227.0

PI(D7) 14 14 100 76.8 100 718.2 442.5 1165.7 Pr-10Pn PIII(M3) 54 13 24.1 13.5 37.6 79.7 61.1 103.9

Pre-Bo 27 9 33.3 16.5 54.0 73.6 58.1 93.2

Post-Bo 29 22 75.9 56.5 89.7 162.9 113.2 234.4

Post-Y1 55 43 78.2 65.0 88.2 224.9 169.6 298.2 Post-Y2 55 38 69.1 55.2 80.9 171.3 129.3 226.8

Post-Y4 54 36 66.7 52.5 78.9 141.6 109.1 183.8

PI(D7) 54 54 100 93.4 100 680.7 522.9 886.2 Unprimed PRE 95 54 56.8 46.3 67.0 106.0 91.1 123.4

PI(D7) 96 92 95.8 89.7 98.9 382.9 320.7 457.2

PII(M3) 98 98 100 96.3 100 708.6 604.6 830.4

N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3) = 1 month after dose III (primary phase)

Pre-Bo = pre-booster vaccination blood sample (booster phase) Post-Bo = post-booster vaccination blood sample (booster phase) Post-Bo (Y1) = 12 months after booster dose Post-Bo (Y2) = 24 months after booster dose Post-Bo (Y4) = 48 months after booster dose PRE= prior to catch-up vaccination PI(D7)= 7 days after additional dose (Primed groups)/ 7 days after dose 1 of the 2-dose catch-up vaccination (Unprimed group) PII(M3)= 1 month after dose 2 of the 2-dose catch-up vaccination

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited local symptom during the 4-day (Days 0-3) post-vaccination period – Primed Subjects (Total Vaccinated cohort)

10Pn Group Prev Group Pr-10Pn Group 95 % CI 95 % CI 95 % CI

Symptom Intensity N n % LL UL N n % LL UL N n % LL UL

Pain Any 264 157 59.5 53.3 65.4 20 9 45.0 23.1 68.5 64 34 53.1 40.2 65.7 Grade 3 264 7 2.7 1.1 5.4 20 1 5.0 0.1 24.9 64 5 7.8 2.6 17.3

Redness Any 264 90 34.1 28.4 40.2 20 5 25.0 8.7 49.1 64 14 21.9 12.5 34.0

>30 mm 264 7 2.7 1.1 5.4 20 0 0.0 0.0 16.8 64 0 0.0 0.0 5.6

Swelling Any 264 67 25.4 20.2 31.1 20 4 20.0 5.7 43.7 64 15 23.4 13.8 35.7 >30 mm 264 5 1.9 0.6 4.4 20 0 0.0 0.0 16.8 64 1 1.6 0.0 8.4

N = number of subjects with the documented dose n (%) = number (percentage) of subjects reporting at least once the symptom 95% CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any local symptom regardless of intensity grade

1. Grade 3 pain = cried when limb was moved/spontaneously painful

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited local symptoms during the 4-day (Days 0-3) post-vaccination period – Unprimed Subjects (Total Vaccinated cohort)

Unprimed Group 95 % CI

Symptom Intensity N n % LL UL

Dose 1 Pain Any 100 50 50.0 39.8 60.2

Grade 3 100 1 1.0 0.0 5.4

Redness Any 100 19 19.0 11.8 28.1

>30 mm 100 0 0.0 0.0 3.6 Swelling Any 100 16 16.0 9.4 24.7

>30 mm 100 2 2.0 0.2 7.0

Dose 2 Pain Any 100 30 30.0 21.2 40.0

Grade 3 100 2 2.0 0.2 7.0

Redness Any 100 7 7.0 2.9 13.9

>30 mm 100 1 1.0 0.0 5.4 Swelling Any 100 5 5.0 1.6 11.3

>30 mm 100 0 0.0 0.0 3.6

Across Doses Pain Any 100 54 54.0 43.7 64.0

Grade 3 100 3 3.0 0.6 8.5

Redness Any 100 21 21.0 13.5 30.3 >30 mm 100 1 1.0 0.0 5.4

Swelling Any 100 20 20.0 12.7 29.2

>30 mm 100 2 2.0 0.2 7.0

N = number of subjects with at least one documented dose n (%) = number (percentage) of subjects reporting at least once the symptom 95%CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any local symptom regardless of intensity grade

1. Grade 3 pain = cried when limb was moved/spontaneously painful

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited general symptoms during the 4-day (Days 0-3) post-vaccination period – Primed Subjects (Total Vaccinated cohort) 10Pn Group Prev Group Pr-10Pn Group

95 % CI 95 % CI 95 % CI

Symptom Intensity/ Relationship

N n % LL UL N n % LL UL N n % LL UL

Drowsiness Any 263 49 18.6 14.1 23.9 20 2 10.0 1.2 31.7 64 12 18.8 10.1 30.5

Grade 3 263 1 0.4 0.0 2.1 20 0 0.0 0.0 16.8 64 0 0.0 0.0 5.6 Related 263 48 18.3 13.8 23.5 20 2 10.0 1.2 31.7 64 11 17.2 8.9 28.7

Irritability Any 263 35 13.3 9.4 18.0 20 4 20.0 5.7 43.7 64 6 9.4 3.5 19.3

Grade 3 263 0 0.0 0.0 1.4 20 0 0.0 0.0 16.8 64 0 0.0 0.0 5.6

Related 263 35 13.3 9.4 18.0 20 4 20.0 5.7 43.7 64 6 9.4 3.5 19.3 Loss of appetite

Any 263 30 11.4 7.8 15.9 20 3 15.0 3.2 37.9 64 6 9.4 3.5 19.3

Grade 3 263 1 0.4 0.0 2.1 20 0 0.0 0.0 16.8 64 1 1.6 0.0 8.4

Related 263 30 11.4 7.8 15.9 20 3 15.0 3.2 37.9 64 5 7.8 2.6 17.3 Fever (Axillary) ≥37.5°C 263 13 4.9 2.7 8.3 20 0 0.0 0.0 16.8 64 2 3.1 0.4 10.8

>39.5°C 263 0 0.0 0.0 1.4 20 0 0.0 0.0 16.8 64 0 0.0 0.0 5.6

Related 263 13 4.9 2.7 8.3 20 0 0.0 0.0 16.8 64 1 1.6 0.0 8.4

N = number of subjects with the documented dose n (%) = number (percentage) of subjects reporting at least once the symptom 95%CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any general symptom regardless of intensity grade and relationship Related = general symptom considered by the investigator to be causally related to the study vaccination Grade 3 drowsiness = drowsiness that prevented normal activity Grade 3 irritability = crying that could not be comforted/ prevented normal activity

1. Grade 3 loss of appetite = did not eat at all

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited general symptoms during the 4-day (Days 0-3) post-vaccination period – Unprimed Subjects (Total vaccinated cohort)

Unprimed Group 95 % CI

Symptom Intensity/ Relationship N n % LL UL

Dose 1 Drowsiness Any 100 7 7.0 2.9 13.9

Grade 3 100 0 0.0 0.0 3.6

Related 100 6 6.0 2.2 12.6 Irritability Any 100 7 7.0 2.9 13.9

Grade 3 100 0 0.0 0.0 3.6

Related 100 7 7.0 2.9 13.9

Loss of appetite Any 100 10 10.0 4.9 17.6 Grade 3 100 0 0.0 0.0 3.6

Related 100 8 8.0 3.5 15.2

Fever (Axillary) ≥37.5°C 100 3 3.0 0.6 8.5 >39.5°C 100 0 0.0 0.0 3.6

Related 100 3 3.0 0.6 8.5

Dose 2

Drowsiness Any 100 6 6.0 2.2 12.6 Grade 3 100 0 0.0 0.0 3.6

Related 100 6 6.0 2.2 12.6

Irritability Any 100 3 3.0 0.6 8.5 Grade 3 100 0 0.0 0.0 3.6

Related 100 3 3.0 0.6 8.5

Loss of appetite Any 100 3 3.0 0.6 8.5 Grade 3 100 0 0.0 0.0 3.6

Related 100 3 3.0 0.6 8.5

Fever (Axillary) ≥37.5°C 100 2 2.0 0.2 7.0

>39.5°C 100 0 0.0 0.0 3.6

Related 100 2 2.0 0.2 7.0

Across Doses Drowsiness Any 100 12 12.0 6.4 20.0

Grade 3 100 0 0.0 0.0 3.6

Related 100 11 11.0 5.6 18.8

Irritability Any 100 8 8.0 3.5 15.2 Grade 3 100 0 0.0 0.0 3.6

Related 100 8 8.0 3.5 15.2

Loss of appetite Any 100 13 13.0 7.1 21.2 Grade 3 100 0 0.0 0.0 3.6

Related 100 11 11.0 5.6 18.8

Fever (Axillary) ≥37.5°C 100 5 5.0 1.6 11.3 >39.5°C 100 0 0.0 0.0 3.6

Related 100 5 5.0 1.6 11.3

N = number of subjects with at least one documented dose n (%) = number (percentage) of subjects reporting at least once the symptom 95%CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any general symptom regardless of intensity grade and relationship Related = general symptom considered by the investigator to be causally related to the study vaccination Grade 3 drowsiness = drowsiness that prevented normal activity Grade 3 irritability= crying that could not be comforted/ prevented normal activity

1. Grade 3 loss of appetite = did not eat at all

Safety Results: Number (%) of subjects with unsolicited AEs reported during the 31-day (Days 0-30) post-vaccination follow-up period (Total Vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination)

10Pn Group N = 264

Prev Group N = 20

Pr-10Pn Group N = 65

Unprimed Group N = 100

Subjects with any AE(s), n (%) 25 (9.5) 0 (0.0) 3 (4.6) 6 (6.0)

Nasopharyngitis 4 (1.5) - 1 (1.5) 1 (1.0) Pharyngitis 5 (1.9) - - 1 (1.0)

Bronchitis 2 (0.8) - - 1 (1.0)

Diarrhoea 2 (0.8) - - - Pyrexia 2 (0.8) - - -

Gastroenteritis - - - 1 (1.0)

Laryngitis - - - 1 (1.0) Rash - - - 1 (1.0)

Tonsillitis - - 1 (1.5) -

Upper respiratory tract infection - - 1 (1.5) -

As there were more than 3 groups, some with more than and others with less than 30 subjects, 2 counting rules were applied:

Prev Group: As there were less than 30 subjects per treatment group, AE that occurs in more than one subject in each treatment group are to be listed.

10Pn, Pr-10Pn and Unprimed groups: As there were more than 30 subjects per treatment group and > 3 groups, only the 5 most frequent events in each treatment group are to be listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 5 most frequent events for that group.

Safety Results: Number (%) of subjects with SAEs reported till the end of the Persistence Analysis– Primed Subjects (Total Enrolled cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication]

All SAEs 10Pn Group N = 316

Prev Group N = 25

Pr-10Pn Group N = 85

Subjects with any SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Fatal SAEs 10Pn Group N = 316

Prev Group N = 25

Pr-10Pn Group N = 85

Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Safety Results: Number (%) of subjects with SAEs reported during the whole study period (Total Vaccinated cohort)

Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs 10Pn

Group N = 264

Prev Group N = 20

Pr-10Pn Group N = 65

Unprimed Group N = 100

Subjects with any SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Fatal SAEs 10Pn Group N = 264

Prev Group N = 20

Pr-10Pn Group N = 65

Unprimed Group N = 100

Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Conclusion: Four years after booster vaccination, for each pneumococcal serotype 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F at least 68.4% of subjects in each group had antibody concentration ≥ 0.05 µg/mL. During the 31-day post-additional dose/catch-up doses period: • In the primed groups, at least one unsolicited symptom was reported for 9.5%, 0.0% and 4.6% of subjects in the 10Pn, Prev and Pr-10Pn groups, respectively. • In the Unprimed group, at least one unsolicited symptom was reported for 6.0% of subjects. No SAEs were reported from Year 2 follow-up until end of Y4 follow-up or after additional dose/catch-up doses up to study end. For conclusions on data of previous time points (Years 1 and 2), please refer to the 111345 and 111346 CTRS.

Date updated: 05-December-2013