Recent Advances in the Development of Inactivated ...Poster 115. IRV-IPV CO-ADMINISTRATION (IM): NO INTERFERENCE & IRV DOSE SPARING. Wang et al, unpublished. IRV-IPV combination vaccine

Recent Advances in the Development of Inactivated Rotavirus Vaccine

Baoming JiangCDC, Atlanta, USA

[email protected]

13th International Rotavirus SymposiumMinsk, Belarus August 30, 2018

Single strain approach -- Simple manufacturing -- Low cost

1. Inactivated viral vaccines are tried and true – e.g., Polio, HAV, ….

2. Inactivated vaccine would be suitable for a combination product

3. Technology to manufacture IRVs are available to emerging manufacturers

4. RV immunity is based on multiple epitopes on multiple gene segments ♦ Children only get one episode of severe RVD (Velazquez)♦ Monovalent vaccines (Rotarix, Rotavac) protect against all serotypes♦ Bovine vaccine ( Vesikari) protected against human strains

G1P8 G2P4

G1P8

>99% TLP

IRV: Human Strain CDC-9 with High Growth & Stability

~ 107 ffu/ml

~ 108 ffu/ml

Vero Cells

● 107 ~ 108 titer in Vero cells ● Predominant (>90%) triple-layered● Stable during USP & DSP

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiuh976vOXOAhWC4SYKHSw_A-kQjRwIBw&url=http://www.coleparmer.com/Product/Corning_roller_bottle_850_cm2_easy_grip_cap/EW-01836-01&psig=AFQjCNH96cIDWnQZArSim18H7PVnMqaVVg&ust=1472520630684635http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjOuvugveXOAhXEJiYKHdDaDcwQjRwIBw&url=http://www.sanisure.com/Products/Single-Use-Bioreactor-Accessory-Kits.aspx&psig=AFQjCNFB6B0uWQPnFf-uIUui0RFi6JkVoQ&ust=1472520710964413

10

100

1000

10000

Wa G1P[8] MW333 G8P[4] WI61 G9P[8]

Antib

odie

s (G

MT)

pre dose 1

post dose 1

post dose 2

post dose 3

A monovalent CDC-9 IRV induces cross neutralizing antibody to homotypic and heterotypic strains

Jiang et al, Human Vaccines & Immunotherapeutics 2013 Wang et al Vaccine 2010

Chart1

Wa G1P[8]Wa G1P[8]Wa G1P[8]Wa G1P[8]0.10.18888314314512512

MW333 G8P[4]MW333 G8P[4]MW333 G8P[4]MW333 G8P[4]0.10.13939157157128128

WI61 G9P[8]WI61 G9P[8]WI61 G9P[8]WI61 G9P[8]0.10.13323231616

pre dose 1

post dose 1

post dose 2

post dose 3

Antibodies (GMT)

20

279

1940

3072

10

160

640

1152

10

15.2

60.6

96

Sheet1

Path Guinea pig serum IgG & MN

DateWa G1P[8]STDERRORMWI333 G8P[4]STDERRORRotaTeq G1P[5]STDERRORWI61(G9)STDERROR

3/14/2011(Pre)Pre176505050

3/24/2011(post 1)Post 1200505050

4/27/2011(post2)Post 22798816039265176.7

5/27/2011(post3)Post 31940314640157160397252.2

Sheet1

�1�1�1�1

6088314

0039157

00539

��

Pre

Post 1

Post 2

Post 3

Sheet2

Path Guinea pig serum IgG & MN

DateSTDERRORWa G1P[8]STDERRORSTDERRORRotaTeq G1P[5]STDERRORRotaTeq G6P[8]STDERRORWC3 G6P[5]STDERROR

3/14/2011(Pre)Pre01760100100100

3/24/2011(dose 1)dose 102000100100134

4/27/2011(dose 2)dose 2960279883265100200

5/27/2011(dose 3)dose 32560194031423160391004010

6/10/2011(post dose 3)Post 3512030725121617639100285

DateWa G1P[8]MW333 G8P[4]WI61 G9P[8]

3/24/2011(dose 1)pre dose 1201010

4/27/2011(dose 2)post dose 127916015.2

5/27/2011(dose 3)post dose 2194064060.6

6/10/2011(post dose 3)post dose 33072115296

STDERRORSTDERRORSTDERROR

3/24/2011(dose 1)dose 10.10.10.1

4/27/2011(dose 2)dose 288393

5/27/2011(dose 3)dose 331415723

6/10/2011(post dose 3)Post 351212816

Sheet2

0.10.18888314314512512

0.10.13939157157128128

0.10.13323231616

pre dose 1

post dose 1

post dose 2

post dose 3

Antibodies (GMT)

Sheet3

IM IRV protects against oral RV challenge in piglets

Wang et al (PLOS One, 2016)

Placebo IRV

RV shedding in stool was measured by EIA

Days after oral challenge

RV

antig

en in

sto

ol (O

D v

alue

)

Chart1

0.0530.0510.045

0.0870.0480.045

0.7320.3890.078

0.8180.3620.284

0.850.4070.317

0.1650.6460.345

0.160.2050.211

0.0680.1810.189

0.0520.0590.084

0.0560.0640.088

11-1

11-2

11-3

Prot 11-13

Derived:06/02/2013Gp11-13

ILACUC -Protocols No.2010A008803/26/2013-03/26/2016PI - Dr Linda SaifNormal sow #G116

IsolatorNo. pigsPig No.Group1st Injection2nd Injection3rd InjectionChallengeEuthanasiaTissues

PORS

131,2,3AAAAAA vaccineAAA vaccineAAA vaccineVirHRV WaPID42Blood, spleen, MLNs

4 placesmicroneedleID microneedleID microneedleID microneedle

PORS

244,5,6,7BBBBBB vaccineBBB vaccineBBB vaccineVirHRV WaPID42Blood, spleen, MLNs


PORS

348,9,10,11CCCCCC vaccineCCC vaccineCCC vaccineVirHRV WaPID42Blood, spleen, MLNs

4 placesIMIMIMIM

PORS, urine

439,10,11DMF+VirHRVDMF 105 CFU/pig eachVirHRV WaPBCD36/PCD21Blood, Duo, Ile, Jej, Col

4 placesCecum, Spleen,

LIC, SIC

`

calendar 11-13

Printed:07/02/13LitterGP- 11-2013PI: Dr. L Saif

SUNDAYMONDAYTUESDAYWEDNESDAYTHURSDAYFRIDAYSATURDAY

30-Jun1-Jul2-Jul3-Jul4-Jul5-Jul6-Jul30-Sep

HysterectomyPID0

RS sterility, Bleed all

1st vaccination

7-Jul8-Jul9-Jul10-Jul11-Jul12-Jul13-Jul


PID10


2nd vaccination


PID21


3rd vaccination

28-Jul29-Jul30-Jul31-Jul1-Aug2-Aug3-Aug

PID28

RS sterility, Bleed allRS all

VirHRV challenge

4-Aug5-Aug6-Aug7-Aug8-Aug9-Aug10-Aug

RS allRS allRS allRS allRS allRS allRS all

Bleed allBleed all

11-Aug12-Aug13-Aug14-Aug15-Aug16-Aug17-Aug23-Feb

PID38PID42

RS allRS allEuthanasia all

Bleed allCollect specimens

21-Sep

15-Jun

13-Jul

20-Jul

24-Aug

LabelC

Protocol #2010A0088Protocol #2010A0088

Date:03/26/2013-03/26/2016Date:03/26/2013-03/26/2016

Title:Immunization of pigs with candidate rotavirus vaccinesTitle:Immunization of pigs with candidate rotavirus vaccines

PI:Dr.Linda SaifPI:Dr.Linda Saif


Date:03/26/2013-03/26/2016Date:03/26/2013-03/26/2016



Isolate 1Isolate 2

GP11-13GP11-13

Pig#1-3Pig#4-7

AAABBB

Isolate 3

GP11-13

Pig#8-11

CCC

Label


Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010




Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010



Isolate 3Isolate 4Isolate 1Isolate 2

Gp05-09Gp05-09Gp05-09Gp05-09

Pig #7-9Pig #10-13Pig #1-3Pig #4-6

ControlControlAttHRV M strainAttHRV M strain

Vit AVit AVit A

diarrhea

MN MockMN IRVIM IRV

11-111-211-311-411-511-611-711-811-911-1011-11

101111111002

200110111201

312110100110

411110000110

512101000101

612200001011

700000000000

800000000000

900000000010

1000000000000

faecal consistency was

scored as follows: 0 = solid; 1 = pasty; 2 = semi-liquid;

3 = liquid, with scores of 2 or more considered diarrhoeic.

diarrhea

11-1

11-2

11-3

Shedding-OD

11-4

11-5

11-6

11-7

Sheet1

11-8

11-9

11-10

11-11

MN MockMN IRVIM IRV

11-111-211-311-411-511-611-711-811-911-1011-11

10.0530.0510.0450.0450.0470.0490.0450.0460.0490.0480.053

20.0870.0480.0450.0480.0510.050.050.0520.0450.0480.046

30.7320.3890.0780.0480.3170.0450.0810.1660.0440.048

40.8180.3620.2840.060.2150.0460.0580.110.0450.0560.048

50.850.4070.3170.0480.2410.060.0590.0740.0450.0580.049

60.1650.6460.3450.0470.0810.0630.0520.0540.0440.0570.044

70.160.2050.2110.0520.0570.0540.0510.0540.0450.0510.05

80.0680.1810.1890.050.050.0460.0510.0530.0540.0460.046

90.0520.0590.0840.0450.050.0490.050.0510.0480.0530.049

100.0560.0640.0880.0470.0490.0730.050.0580.0560.0670.053

11-1

11-2

11-3

11-4

11-5

11-6

11-7

11-8

11-9

11-10

11-11

Chart1

0.0460.0490.0480.053

0.0520.0450.0480.046

0.1660.0440.048

0.110.0450.0560.048

0.0740.0450.0580.049

0.0540.0440.0570.044

0.0540.0450.0510.05

0.0530.0540.0460.046

0.0510.0480.0530.049

0.0580.0560.0670.053

11-8

11-9

11-10

11-11

Prot 11-13

Derived:06/02/2013Gp11-13

ILACUC -Protocols No.2010A008803/26/2013-03/26/2016PI - Dr Linda SaifNormal sow #G116

IsolatorNo. pigsPig No.Group1st Injection2nd Injection3rd InjectionChallengeEuthanasiaTissues

PORS

131,2,3AAAAAA vaccineAAA vaccineAAA vaccineVirHRV WaPID42Blood, spleen, MLNs


PORS

244,5,6,7BBBBBB vaccineBBB vaccineBBB vaccineVirHRV WaPID42Blood, spleen, MLNs


PORS

348,9,10,11CCCCCC vaccineCCC vaccineCCC vaccineVirHRV WaPID42Blood, spleen, MLNs

4 placesIMIMIMIM

PORS, urine

439,10,11DMF+VirHRVDMF 105 CFU/pig eachVirHRV WaPBCD36/PCD21Blood, Duo, Ile, Jej, Col

4 placesCecum, Spleen,

LIC, SIC

`

calendar 11-13

Printed:07/02/13LitterGP- 11-2013PI: Dr. L Saif

SUNDAYMONDAYTUESDAYWEDNESDAYTHURSDAYFRIDAYSATURDAY

30-Jun1-Jul2-Jul3-Jul4-Jul5-Jul6-Jul30-Sep

HysterectomyPID0


1st vaccination



PID10


2nd vaccination


PID21


3rd vaccination

28-Jul29-Jul30-Jul31-Jul1-Aug2-Aug3-Aug

PID28

RS sterility, Bleed allRS all

VirHRV challenge

4-Aug5-Aug6-Aug7-Aug8-Aug9-Aug10-Aug

RS allRS allRS allRS allRS allRS allRS all

Bleed allBleed all

11-Aug12-Aug13-Aug14-Aug15-Aug16-Aug17-Aug23-Feb

PID38PID42

RS allRS allEuthanasia all

Bleed allCollect specimens

21-Sep

15-Jun

13-Jul

20-Jul

24-Aug

LabelC


Date:03/26/2013-03/26/2016Date:03/26/2013-03/26/2016




Date:03/26/2013-03/26/2016Date:03/26/2013-03/26/2016



Isolate 1Isolate 2

GP11-13GP11-13

Pig#1-3Pig#4-7

AAABBB

Isolate 3

GP11-13

Pig#8-11

CCC

Label


Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010




Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010



Isolate 3Isolate 4Isolate 1Isolate 2

Gp05-09Gp05-09Gp05-09Gp05-09

Pig #7-9Pig #10-13Pig #1-3Pig #4-6

ControlControlAttHRV M strainAttHRV M strain

Vit AVit AVit A

diarrhea

MN MockMN IRVIM IRV

11-111-211-311-411-511-611-711-811-911-1011-11

101111111002

200110111201

312110100110

411110000110

512101000101

612200001011

700000000000

800000000000

900000000010

1000000000000

faecal consistency was

scored as follows: 0 = solid; 1 = pasty; 2 = semi-liquid;

3 = liquid, with scores of 2 or more considered diarrhoeic.

diarrhea

11-1

11-2

11-3

Shedding-OD

11-4

11-5

11-6

11-7

Sheet1

11-8

11-9

11-10

11-11

MN MockMN IRVIM IRV

11-111-211-311-411-511-611-711-811-911-1011-11

10.0530.0510.0450.0450.0470.0490.0450.0460.0490.0480.053

20.0870.0480.0450.0480.0510.050.050.0520.0450.0480.046

30.7320.3890.0780.0480.3170.0450.0810.1660.0440.048

40.8180.3620.2840.060.2150.0460.0580.110.0450.0560.048

50.850.4070.3170.0480.2410.060.0590.0740.0450.0580.049

60.1650.6460.3450.0470.0810.0630.0520.0540.0440.0570.044

70.160.2050.2110.0520.0570.0540.0510.0540.0450.0510.05

80.0680.1810.1890.050.050.0460.0510.0530.0540.0460.046

90.0520.0590.0840.0450.050.0490.050.0510.0480.0530.049

100.0560.0640.0880.0470.0490.0730.050.0580.0560.0670.053

11-1

11-2

11-3

11-4

11-5

11-6

11-7

11-8

11-9

11-10

11-11

Long

-term

Sto

rage

Con

ditio

n

Acce

lera

ted

Stor

age

Cond

ition

Poster 75

IRV formulations are highly stable and potent in vitro

Three IRV lots stable for 12 month at 4 C & 6 month at 37 C

♦Protein concentration ♦pH♦Osmolarity

7

• Strong IRV candidate – High growth– High structural integrity (TLPs)– High stability at 4 C and 37 C

• IM IRV: strong proof of concept in animals– Dose sparing– Highly immunogenic

• Cross-neutralizing antibody (homotypic & heterotypic strains)• Intestinal immunity

– Protective efficacy against infection & disease

Summary -- I

IRV clinical development is in progress

Combination vaccine

Crowded childhood immunization schedules

USA

India

China

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=imgres&cd=&cad=rja&uact=8&ved=2ahUKEwj_4s_K3_TcAhVB-6wKHbu-DoYQjRx6BAgBEAU&url=https%3A%2F%2Fwww.parentlane.com%2Fhealth%2Fbaby-health%2Fvaccination-chart-newborn-baby&psig=AOvVaw1Z7NFyhUqnzV_CySOKACn6&ust=1534617972821074https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=2ahUKEwi4sc_44fTcAhUH1qwKHc4xCD0QjRx6BAgBEAU&url=https%3A%2F%2Fwww.beijing-kids.com%2Fblog%2F2016%2F10%2F27%2Fthe-china-vaccination-guide-what-new-beijing-expats-need-to-know%2F&psig=AOvVaw180hTQ9Y2AaYPgH7Q0NBUF&ust=1534618523747141https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=2ahUKEwjfvY_64_TcAhUKVa0KHQLoCbYQjRx6BAgBEAU&url=https%3A%2F%2Fvaxopedia.org%2F2017%2F04%2F23%2Fimmunization-schedules-from-other-countries%2F&psig=AOvVaw1zSvKtdQYEqZwlVo8RSk7L&ust=1534619119350270

Rota and Polio Vaccines

Characteristics Polio RotaEpidemiology - Infects at younger age in LIC

- Year round disease in LIC- Higher case-fatality in LIC

Immunity - Intestinal & humoral immunity both involved for protection- Both oral vaccines are less effective in LICSerotype-specific Cross-reactive

Safety (oral vaccine)

Rare cases of polio (VAPP, VDPV)

Rare cases of intussusception and revertant strains

Immunization schedule

6, 10, 14 week or3, 4, 5 month

Manufacturing Vero cell platform: similar USP & DSP

11

• No need for a new vial and a separate cold chain – Simplify administration– Keep cost down

• Complement pentavalent vaccine (cheap)• New IPV formulation

– Dose sparing– Help vaccine shortage

• Insurance: – Protection against polio that may not exist– IRV adds value

• Polio eradication/endgame– Current: 1-3 doses for IPV, 2 or 3 doses for RV – Future: WHO recommends 2 doses IPV

RATIONALE FOR A COMBINED IRV-IPV

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjF4YC8vPfcAhVFOK0KHbzZCXAQjRx6BAgBEAU&url=http%3A%2F%2Fsmokieclennell.blogspot.com%2F2014%2F03%2Flow-hanging-fruit.html&psig=AOvVaw35t7XqXPCTfcf4pir7xkNN&ust=1534711617594521

WHO SAGE IPV recommendation after global OPV withdraw

1st dose6 wk

2nd dose10 wk

3rd dose14 wk

OPV OPV IPV

1st dose2 mo

2nd dose4 mo

3rd dose6 mo

IPV IPV IPV

1st dose10-14 wk

2nd dose9 mo

IPV IPV

Developing countries Developed countries

IRV-IPV CO-ADMINISTRATION (IM): NO INTERFERENCE & IPV DOSE SPARING

Y Wang et al, unpublished

Poster 115

https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjVtLfZhovbAhVQs1kKHTvaAo0QjRx6BAgBEAU&url=http://www.brandsoftheworld.com/logo/cdc-2&psig=AOvVaw2a-J6vsmrRNZ2-ZTpGJaQQ&ust=1526588292634619Chart1

IRV100%IRV100%IRV100%IRV100%00000000

IRV+IPVIRV+IPVIRV+IPVIRV+IPV001.111.111.061.060.120.12

IPVIPVIPVIPV000.840.840000

IRV25%IRV25%IRV25%IRV25%00000000

IRV+IPVIRV+IPVIRV+IPVIRV+IPV001.71.70.650.650.680.68

IPVIPVIPVIPV000.420.421.871.870.170.17

IRV+IPV50%IRV+IPV50%IRV+IPV50%IRV+IPV50%001.281.281.261.260.460.46

PlaceboPlaceboPlaceboPlacebo00000000

T0

Post dose1

Post dose 2

Post dose 3

Log2 Neutralization titer (GMT±SEM)

Sabin 1

2.5

2.5

2.5

2.5

2.5

5.4

7.7

8.4

2.5

4.2

10.5

10.5

2.5

2.5

2.5

2.5

2.5

5.5

8.7

9.1

2.5

2.8

7

10

2.5

4.8

7

9.5

2.5

2.5

2.5

2.5

Sheet1

SpecimenIDDate of seraPatientIDSabin 1Sabin 2Sabin 3Mneut-WaMneut-Wa GMT

IF-A1 (8-21-17)8/21/17IF-A1-02.52.52.5

IRV-IPV CO-ADMINISTRATION (IM): NO INTERFERENCE & IRV DOSE SPARING

Wang et al, unpublished

https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjVtLfZhovbAhVQs1kKHTvaAo0QjRx6BAgBEAU&url=http://www.brandsoftheworld.com/logo/cdc-2&psig=AOvVaw2a-J6vsmrRNZ2-ZTpGJaQQ&ust=1526588292634619

IRV-IPV combination vaccine for skin immunization using a skin patch

Micron’s microneedle patch simplifies andimproves the delivery of vaccines

• Targets delivery of vaccines to skin• Simple to administer (minimally-trained personnel or self-administration)• No applicator• Thermal stability (potential to reduce or eliminate cold chain)• Sharps-free waste• Painless

17

• Lack of interference between IPV and IRV

• Dose sparing for both IRV and IPV

• Proof of concept for co-administration in animals– Highly immunogenic– Protective efficacy against infection & disease

• Pilot manufacturing process established

• Clinical trials in partnership with manufacturers

Summary – II (IRV-IPV combination vaccine)

Proposed oral & parenteral vaccination for polio and rota

1st dose 2nd/3rd dose

ORV (6-8 wk)

IRV-IPV (10-14 wk,

9 mo)

IPV-IRV combination vaccine -- boost immunity & enhance protection against RV-- reduce intussusception risk-- insurance for polio eradication/endgame


SERUM INSTITUTE: IRV DEVELOPMENT PROGRESS

Procurement of strains and related regulatory work completed.Preparation and characterization of seed viruses completed.Production procedure (pilot scale) standardized.Inactivation kinetic study on pilot scale (one liter) completed.Immunogenicity & cross protective immunity in animals established.Assays validated, stability and potency completed.

Future plans• Large scale production development process optimization (one year).• Animal Toxicity materials preparation (six months).• Combination vaccine R&D.• First in human study should start by mid 2019.


CHONGQING ZHIFEI BIOLOGICAL PRODUCTS COZhifei was founded in 2002 (rank 2nd among bio-pharma in China)Strong R&D and Manufacturing capability (Beijing, He Fei)Diversified product portfolio (e.g., AC-Hib and TB vaccine)Most competitive strong sales forceSole sales agent of MSD vaccines in China - HPV vaccines, RotaTeq etc.

IRV program (Beijing LvZhu)• Procurement of strains and related regulatory work completed• Preparation and characterization of seed viruses completed• Production procedure, including inactivation, standardized• Immunogenicity in animals established• Assays validated, stability and potency completed• Animal toxicity in progress.• First in human study should start by 2020.


Linda SaifMark PrausnitzStephen Harrison

A c k n o w l e d g m e n t s

Roger Glass Ralph TrippHarry Greenberg

http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwjF9NfX6__OAhVBEpQKHYdJCrEQjRwIBw&url=http%3A%2F%2Facer.dvrlists.com%2Fstanford-university-logo-2%2F&psig=AFQjCNFQzlU7XQRsrNIBvz1TP2aVb30eSw&ust=1473426459669681https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjsvNPU7ZLdAhXDWCwKHbhZDFEQjRx6BAgBEAU&url=https%3A%2F%2Fwww.logolynx.com%2Ftopic%2Fharvard%2Buniversity&psig=AOvVaw2cGQ-GeSn9EXMucXqYnz4r&ust=1535652400737337http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiU8Kbw7pLdAhUDkywKHaTDCdgQjRx6BAgBEAU&url=http%3A%2F%2Fwww.bartlettareavision.com%2Flife-sciences.html&psig=AOvVaw0eIO-PY8I63gftEGfPwaNi&ust=1535652863213730

Recent Advances in the Development of �Inactivated Rotavirus VaccineSlide Number 2Slide Number 3Slide Number 4Slide Number 5Slide Number 6Summary -- ICombination vaccine Crowded childhood immunization schedules Rota and Polio Vaccines Rationale for a combined IRV-IPV WHO SAGE IPV recommendation after global OPV withdraw Slide Number 13Slide Number 14IRV-IPV combination vaccine for skin immunization using a skin patchMicron’s microneedle patch simplifies and�improves the delivery of vaccinesSummary – II (IRV-IPV combination vaccine)Proposed oral & parenteral vaccination for polio and rota serum institute: IRV development progressChongqing Zhifei Biological Products CoAcknowledgments

Documents

Recent Advances in the Development of Inactivated ...Poster 115. IRV-IPV CO-ADMINISTRATION (IM): NO INTERFERENCE & IRV DOSE SPARING. Wang et al, unpublished. IRV-IPV combination vaccine