-
Recent Advances in the Development of Inactivated Rotavirus Vaccine
Baoming JiangCDC, Atlanta, USA
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
4 placesmicroneedleID microneedleID microneedleID microneedle
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
14-Jul15-Jul16-Jul17-Jul18-Jul19-Jul20-Jul
PID10
RS sterility, Bleed all
2nd vaccination
21-Jul22-Jul23-Jul24-Jul25-Jul26-Jul27-Jul
PID21
RS sterility, Bleed all
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
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
Isolate 1Isolate 2
GP11-13GP11-13
Pig#1-3Pig#4-7
AAABBB
Isolate 3
GP11-13
Pig#8-11
CCC
Label
Protocol #2007A0137Protocol #2007A0137
Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010
Title:Immunization of pigs with candidate rotavirus vaccinesTitle:Immunization of pigs with candidate rotavirus vaccines
PI:Dr.Linda SaifPI:Dr.Linda Saif
Protocol #2007A0137Protocol #2007A0137
Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010
Title:Immunization of pigs with candidate rotavirus vaccinesTitle:Immunization of pigs with candidate rotavirus vaccines
PI:Dr.Linda SaifPI:Dr.Linda Saif
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
4 placesmicroneedleID microneedleID microneedleID microneedle
PORS
244,5,6,7BBBBBB vaccineBBB vaccineBBB vaccineVirHRV WaPID42Blood, spleen, MLNs
4 placesmicroneedleID microneedleID microneedleID microneedle
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
14-Jul15-Jul16-Jul17-Jul18-Jul19-Jul20-Jul
PID10
RS sterility, Bleed all
2nd vaccination
21-Jul22-Jul23-Jul24-Jul25-Jul26-Jul27-Jul
PID21
RS sterility, Bleed all
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
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
Isolate 1Isolate 2
GP11-13GP11-13
Pig#1-3Pig#4-7
AAABBB
Isolate 3
GP11-13
Pig#8-11
CCC
Label
Protocol #2007A0137Protocol #2007A0137
Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010
Title:Immunization of pigs with candidate rotavirus vaccinesTitle:Immunization of pigs with candidate rotavirus vaccines
PI:Dr.Linda SaifPI:Dr.Linda Saif
Protocol #2007A0137Protocol #2007A0137
Date:6/21/07 to 6/21/2010Date:6/21/07 to 6/21/2010
Title:Immunization of pigs with candidate rotavirus vaccinesTitle:Immunization of pigs with candidate rotavirus vaccines
PI:Dr.Linda SaifPI:Dr.Linda Saif
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
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
-
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.
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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.
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Linda SaifMark PrausnitzStephen Harrison
A c k n o w l e d g m e n t s
Roger Glass Ralph TrippHarry Greenberg
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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