Impact of a Quadrivalent Conjugate (MenACWY-CRM) or a Serogroup B (4CMenB) Meningococcal Vaccine on Meningococcal Carriage in English University Students

Robert C. Read and Colleagues

• Phase III, multi-centre, RCT

• 2,968 students from universities at 10 different UK sites

• 3 month enrolment (Sep–Dec 2010)

• Subjects received either:

– 2 doses of 4CMenB (BEXSERO)

– 1 dose of MenACWY-CRM (MENVEO)/1 dose of saline placebo

– 2 doses of Japanese encephalitis (IXIARO) (control)

• Nasopharyngeal swabs taken at baseline, and at Months 1, 2, 4, 6 and 12

• Carriage isolate characterisation performed at HPA (PHE) and Oxford University

Study MethodsPre-licensure study to assess effect on carriage at an individual level

Primary Analysis at 1 Month After the Vaccination Series

Vaccine GroupsEfficacy %(95% CI)MenACWY-CRM Control

Visit 2[Month 1]

Number 56 58 16.0%

(-27.3 – 44.5)% 5.87% 6.12%

N 954 947

MenACWY-CRM co-primary Carriage prevalence of N. meningitidis combined serogroups A, C, W and Y at 1 month following administration of a single dose of MenACWY-CRM

Vaccine GroupsEfficacy %(95% CI)4CMenB Control

Visit 3[Month 2]

Number 87 75 -18.2%

(-73.3 – 19.4)% 9.50% 8.08%

N 916 928

4CMenB co-primary Carriage prevalence of virulent sequence types (ST)* of N. meningitidis capsular group B at 1 month following administration of 2 doses of 4CMenB

*Virulent ST types are those capsular group B ST types (or clonal complex members) causing disease in the UK (2006-2010).

Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.

Vaccine GroupsEfficacy %(95% CI)MenACWY-

CRM Control

C, W, YSerogroupable

Number 193 26036.2%

(15.6 – 51.7)% 5.5% 7.4%

N 3520 3504

MenACWY-CRM – Carriage at Cumulative Later Sampling Points

MenACWY-CRM secondary Carriage prevalence and calculated efficacy of combined serogroups CWY and serogroup Y across cumulative later timepoints (Visits 3–6)

MenACWY-CRM reduces nasopharyngeal carriage of N. meningitidis serogroup CWY strains

YSerogroupable

Number 157 227

39.0%

(17.3 – 55.0)

% 4.5% 6.5%

N 3520 3504

Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.

4CMenB– Carriage at Cumulative Later Sampling Points4CMenB secondary Carriage prevalence and calculated efficacy for carriage of combined capsular groups BCWY or all N. meningitidis strains across cumulative later timepoints (Visits 4–6)

Any N. meningitidis

Number 797 885

18.2%

(3.4 – 30.8)

% 32.0% 34.4%

N 2489 2576

Vaccine GroupsEfficacy %(95% CI)4CMenB Control

B, C, W, Y Capsular group

Number 449 53926.6%

(10.5 – 39.9)% 18.0% 20.9%

N 2489 2576

4CMenB reduces nasopharyngeal carriage of N. meningitidis capsular group BCWY strains

Non-significant trends for virulent B strains (12.6%; p=0.350) and all ST B strains (15.6%; p=0.225)

Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.

• In all risk factor groups, although trends were evident for efficacy against virulent B strains and all ST B strains, statistical significance was not met.

B, C, W, Y Capsular group Any N. meningitidis

Efficacy %(95% CI)

Efficacy %(95% CI)

Early Enrollers (<30 Days After Start of the Semester)

N=1022 – 1031

32.0%

(8.2 – 49.6)

33.7%

(13.9 – 49.0)

SmokersN=320 – 425

44.8%

(14.0 – 64.5)

32.2%

(2.5 – 52.9)

4CMenB – Exploratory AnalysisRisk Factor Groups With High Transmission/Acquisition4CMenB secondary Carriage prevalence and calculated efficacy for carriage of combined capsular groups BCWY or all N. meningitidis strains across cumulative later timepoints (Visits 4–6)

Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.

• Primary objectives were not achieved for either MenACWY-CRM or 4CMenB

• MenACWY-CRM: Secondary analyses demonstrated an impact on carriage of CWY combined

• 4CMenB: Secondary analyses demonstrated an impact on carriage of BCWY combined and any N. meningitidis

– Effect apparently enhanced among groups at high risk for transmission

– Trends observed in carriage impact and new acquisition of MenB strains

• Overall results support a possible herd impact by both vaccines

• Only post-implementation surveys within large scale vaccination programs will determine fully the population level impact of these vaccines

Conclusions

Acknowledgements

• Clinical Research Facility staff at Sheffield, Liverpool, Manchester, Middlesbrough, Oxford, Southampton, Bristol, St George’s, Guildford, Nottingham

• UK National Institute of Health Clinical Research Network (NIHR CRN)

• Public Health England• Novartis Vaccines and Diagnostics

10

David BaxterRohit BazazRay BorrowDavid R. ChadwickPeter M. DullSaul N. FaustAdam Finn

Tav GanguliStefanie GilchristStephen GordonSteve J. GrayTom HavelockT. HeathClaudia Kittel

J.M. LewisMaggie McCarthyBegonia Morales-AzaKeith R. NealIfeanyichukwu OkikeKamlesh PatelAndrew J. Pollard

Robert ReadMatthew D. SnapeDavid P.J. TurnerJohn Williams