Zyvac TCV, the new Typhoid Conjugate vaccine by Zydus Vaccines with Indian TT conjugate protein. Comparison with Bharat Biotech Typhoid Vaccine

1. The new generation ‘Indian’ TCV
Zyvac-TCV
Dr. Gaurav Gupta,
Charak Clinics, Mohali
for Panchkula, 23 May 2018

2. Conflict of Interest

3. Scope
• Need for Typhoid Vaccine
• TCV v/s ViPS
• Choosing ‘right’ TCV
• Recommendations
• Zydus Vaccines

4. Global burden of typhoid fever

6. MDR typhoid fever (MDRTF) in the last
15 yrs: India
• Incidence of MDRTF: Increased from 34% in 1999 to 66% in 2005
• Mortality during MDRTF epidemics: 7% to 16% (much higher than seen in susceptible typhoid
fever, 2%)
• Increased incidence of complications
Source: Zaki SA, Karande S. Multidrug-resistant typhoid fever: a review. J Infect Dev Ctries. 2011 May 28;5(5):324-37.
6

7. Typhoid Vaccines

8. New generation typhoid vaccines
Typhoid
vaccine
Parenteral
Vi-polysaccharide (Vi-
PS)
Vi-Polysaccharide
Conjugate vaccines
Conjugated with
Pseudomonas
aeruginosa exotoxin A
(not available in India)
Conjugated with
Tetanus Toxoid
Oral
(Not available in India)
Source: Ajay Kalra, Vipin M. Vashishtha. 3.11 TYPHOID VACCINES. IAP Guidebook on Immunization 2013–14. page no 257-270
Conjugated with
Tetanus Toxoid
(25mcg)
Conjugated with
Tetanus Toxoid
(5 mcg)

9. Polysaccharide v/s Conjugate
ViPS TCV
< 2 yr poorly immunogenic > 6 mo
Poor quality Abs High quality Abs
No Booster Effect Good booster effect
Hyporesponsiveness to rpt doses No hyporesponsiveness

10. ZYVAC TCV
CLINICAL TRIAL
PHASE II / III CLINICAL TRIAL
RESULTS: IMMUNOGENICITY &
SAFETY
10CTRI/2016/05/006975
ZyVac TCV composition: Each dose of 0.5 ml contains:
Purified Vi-capsular polysaccharide of S.typhi 25 μg.
conjugated to Tetanus toxoid (Carrier protein) 16 to 50 μg
2-Phenoxyethanol (as preservative) 2.50 mg, Isotonic buffer solution q.s.

11. Typhoid Vi Conjugate Vaccine I.P.
Details of CT sites
3-May-18
Sr.
No.
Name of Investigator Institute
Ped /
Adult
Govt /
Private
1 Dr. Uma Nayak
GMERS Medical College & General
Hospital, Vadodara
Ped Govt
2 Dr. Ritabrata Kudnu Institute of Child Health, Kolkata Ped Govt
3 Dr. T.Ramesh Babu
Gandhi Medical College & Hospital,
Secunderabad
Ped Govt
4 Dr. Vimal Kant Goyal Panchsheel Hospital, Delhi Ped Private
5
Dr. Sanjay Kumar
Jangid
Hi-Tech Medical College & Hospital,
Bhubaneswar
Adult Private
6 Dr. Shrikant Sharma SMS Medical College & Hospital, Jaipur Adult Govt
7
Dr. AmbroseKumar
Kandulna
GCS Medical College & Hospital,
Ahmedabad
Adult Govt
8 Dr. Rajesh Vukkala Indo-US Hospital, Hyderabad Adult Private
9

12. 4
FLOW CHART OF THE STUDY
Typhoid Vi conjugate vaccine of M/s CHL
Typhoid Vi conjugate vaccine of M/s BBIL
Visit 1 2 3 4
Day Day 0 Day 7 ±
3 days
Day 21 ±
7 days
Day 42 +
14 days
Screening &
Randomization
Follow-up Follow-up End of study
3-May-18

13. Typhoid Vi Conjugate Vaccine I.P.
Immunogenicity Results
Primary Immunogenicity Endpoint
% subjects with seroconversion at the end of study
Parameter
Test group
(N = 116)
Reference group
(N = 119)
Test – Reference*
Seroconversion Rate 110 (94.8%) 109 (91.6%)
3.2%
(-3.2% to 9.7%)
Data presented as n (%)
* Difference between proportions (95% CI)
P=0.44 (Fisher’s exact test; test group vs. reference group)
Seroconversion denotes ≥ 4-fold rise in antibody titre post-vaccination

14. Typhoid Vi Conjugate Vaccine I.P.
Immunogenicity Results
Secondary Immunogenicity Endpoint
% subjects in the Adult cohort with
seroconversion at the end of study
Parameter
Test group
(N = 58)
Reference group
(N = 60)
Test – Reference*
Seroconversion Rate 56 (96.6%) 55 (91.7%)
4.9%
(-3.5% to 13.3 %)
Data presented as n (%)
* Difference between proportions (95% CI)
P=0.44 (Fisher’s exact test; test group vs. reference group)

15. Typhoid Vi Conjugate Vaccine I.P.
Immunogenicity Results
Secondary Immunogenicity Endpoint
% subjects in the Pediatric cohort with
seroconversion at the end of study
Parameter
Test group
(N = 58)
Reference group
(N = 59)
Test – Reference*
Seroconversion Rate 54 (93.1%) 54 (91.5%)
1.6%
(-8.1% to 11.2%)
Data presented as n (%)
* Difference between proportions (95% CI)
P=1.0 (Fisher’s exact test; test group vs. reference group)

16. Typhoid Vi Conjugate Vaccine I.P.
Safety Results
• All the AEs resolved completely during the study period
• No SAE was reported during the study period
• INDIAN CARRIER PROTEIN (TT) could result in significantly less Adverse
Events as compared to IMPORTED CARRIER PROTEIN(TT)
Parameter
Test group
(N = 119)
Reference group
(N = 121)
No. (%) of subjects with AEs* 40 (33.6%) 53 (43.8%)
No. of AEs reported 59 93
*P=0.11 (Fisher’s Exact Test; Test group vs. Reference group)

17. Typhoid Vi Conjugate Vaccine I.P.
Safety Results
17
Test group
(N = 119)
Reference group
(N = 121)
P value#
No. of AEs reported* 59 93 ---
Local AEs 39 49 ---
Pain 30 (25.2%) 39 (32.2%) 0.26
Swelling 5 (4.2%) 6 (5.0%) 1.0
Redness 4 (3.4%) 3 (2.5%) 0.72
Irritation 0 (0.0%) 1 (0.8%) 0.32
Systemic AEs 20 44 ---
Fever 7 (5.9%) 17 (14.1%) 0.05
Diarrhoea 3 (2.5%) 1 (0.8%) 0.37
Cold 2 (1.7%) 4 (3.3%) 0.68
Myalgia 2 (1.7%) 6 (5.0%) 0.28
Malaise 1 (0.8%) 4 (3.3%) 0.37
Headache 1 (0.8%) 2 (1.7%) 1.0
Arthralgia 1 (0.8%) 2 (1.7%) 1.0
Vomiting 1 (0.8%) 2 (1.7%) 1.0
Nausea 1 (0.8%) 0 (0.0%) 0.50
URTI 1 (0.8%) 0 (0.0%) 0.50
Cough 0 (0.0%) 2 (1.7%) 0.50
Running nose 0 (0.0%) 2 (1.7%) 0.50
Urticaria 0 (0.0%) 2 (1.7%) 0.50
Data presented as n(%) unless specified; % calculated from No. of events
*Data presented as No. of events
# Chi Square test/Fisher’s Exact test (test group vs. reference group)

18. Typhoid Vi Conjugate Vaccine I.P.
Conclusion
• This randomized, single-blind, multicentre clinical trial suggest
that Typhoid Vi conjugate vaccine of M/s. Cadila Healthcare
Ltd. is non-inferior to Typhoid Vi conjugate vaccine of M/s.
Bharat Biotech International Ltd.
• The test vaccine is immunogenic, well tolerated and its
adverse event profile is similar to the reference vaccine.
18

19. Guidelines

20. WHO Typhoid Position paper - 2018
Primary vaccination
• Higher and more sustained levels of immunogenicity from one dose
of TCV v/s ViPS.
• WHO recommends TCV as a single dose from 6 mo to 45 yr in
Endemic countries.
• WHO encourages routine programmatic administration of TCV at
the same time as other vaccine visits at 9 months of age or in the
second year of life
Catch-up vaccination
• With TCV up to 15 years of age is recommended as burden of
disease and programmatic feasibility are greater in this age range
than in adults
World Health Organization . Typhoid vaccines: WHO position paper, March 2018 – Recommendations. Vaccine (2018),

21. WHO Typhoid Position paper - 2018
Vaccine use in outbreaks and emergency settings
• Recommended
Revaccination
• With TCV Unclear
Vaccination of special populations, contraindications and precautions
• Professional food handlers
• Travellers from non-endemic to endemic areas
• Health-care workers
• Vaccination of pregnant women
• Vaccination of HIV-infected and other immunocompromised
persons

22. Zydus Vaccines

25. Vaccine Manufacturing Capabilities
▪ Spread over a
area of 2005 m2 a
dedicated facility
for production of
Mumps, Measles,
Rubella and
Varicella vaccines.
Live viral
Vaccine
▪ Spread over a
area of 1000 m2 a
dedicated facility
for Recombinant
vaccines like
Hepatitis B and
HPV.
Recombinant
Vaccines
Influenza Vaccines
▪ Dedicated facility
for Influenza
vaccine (Split).
▪ Fully automated
egg inoculation
and harvesting.
• Fill & Finish
(Ampoule , Vial &
PFS Filling line)
Capacity :
▪ 30.0 Mi. Doses per
annum for vial
filling line (multi
dose).
Bacterial Vaccines
25Confidential

26. Vaccine Pipeline: Early Stages
26
Vaccine Pipeline: Advance
Typhoid Conjugate

27. • How effective is the TCV vaccine?
• With a single dose how long would TCV
remain effective?
• With 2 doses appropriately spaced, how long
would TCV remain effective?
• Which TCV should be used ?
FAQs

28. Treatment for Nipah virus found!
Drink 60ml of this anti-bat syrup before sleep

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