Comparisons of different rotavirus vaccines are difficult to make with a lot of precision because of the differing populations, protocols, attack rates, and study procedures which have been employed to assess the efficacy of the vaccines. Given the rather recent deployment of the vaccines, there are very limited evidence on their effectiveness in the population/community-setting.
Type Live attenuated vaccine Live attenuated vaccine
Composition Monovalent liquid frozen vaccine containing live rotavirus 116E strain [G9 P(11)] prepared in Vero cells The vaccine contains serotypes G1, G2, G3, G4 and G9.
Manufacturer Bharat Biotech, India Serum Institute, India
Constituents Naturally occurring reassortant containing one bovine rotavirus gene P(11) and ten human rotavirus gene. Bovine rotavirus UK-Compton strain (G6P5[7]) is the backbone. Different VP7 encoding genes to generate different G-types (G1, G2, G3, G4 & G9).
Route of Administration Oral, liquid Oral, liquid
Dosing schedule Rotavac should be given in a 3 dose series starting at 6 weeks at 4-week intervals. Rotavac may be given together with the other routine childhood vaccinations. Rotasiil is given in a 3-dose schedule, where the first dose is provided at the age of 6 weeks, and subsequent doses are given at 4-week intervals.
Immunogenicity or Efficacy • India: (1) • Niger study:(5)
– Vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) – Per protocol analysis: Vaccine efficacy of 66.7% (95% CI 49.9 to 77.9)
– In the first year of life 56·4% (36·6-70·1; p<0·0001) – Intention to treat analysis: Vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7)
– Number needed to prevent one severe RVGE case: 55 (95% CI 37-97)
• Ongoing Phase III trial (SIIPL presentation) (6)
• India: (2) – No solicited reactions within 7 days of post- vaccination.
– Vaccine efficacy against severe RVGE in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p < 0.0001) – No unsolicited and serious adverse events within 28 days after vaccination.
– Vaccine efficacy in the second year of life was 48.9% (95% CI 17.4 to 68.4; p = 0.0056) – Study completion around Q2 2017
– Number needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0).
• Awaiting publication: (personal communication from Kanungo S)
Immunogenicity: – Vaccine efficacy 36% (95% CI: 11.7-53.6%, p=0.0067) against SRVGE
– Serum IgA seroconversion rates were 73%, and 20% in the 116E and placebo groups, respectively. (3) – Vaccine efficacy 60.5% (95% CI:17.7-81.0%, p=0.0131) against very SRVGE.
– A 4-fold increase in rotavirus immunoglobulin A titer was observed in 66.7% and 64.5% of infants after the first administration and in 62.1% and 89.7% of infants after 3 administrations of doses of 104 ffu and 105 ffu, respectively. (4)
Safety profile and Adverse Events Following Immunization • India:(1) • Awaiting publication: (personal communication from Kanungo S)
– Six (<1%) cases of intussusception were reported in the vaccine group and two (<1%) were reported in the placebo group: difference NOT statistically significant – Incidence of solicited, unsolicited and serious adverse events were similar in both the groups.
– No statistically significant difference in severe adverse events between vaccine and placebo groups. – A total of 1722 SAEs were reported in 1318 subjects (17.5%) by the time of primary analysis; they were experienced by 644 (17.17%) subjects in the BRV-PV group and 674 (17.97%) subjects in the Placebo group.
– No vaccine-related deaths
• India: (7)
– Incidence rate of confirmed intussusception among vac- cine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving placebo. No temporal association; not statistically significant (p = 0.76).
Current status of product WHO prequalified WHO prequalified
References:
- Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet [Internet]. 2014 Jun [cited 2017 Jul 18];383(9935):2136–43. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673613626306
- Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life for the India Rotavirus Vaccine Group. Vaccine [Internet]. 2014;32:A110–6. Available from: http://dx.doi.org/10.1016/j.vaccine.2014.04.079
- Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, et al. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: Results of a randomised controlled trial. Vaccine. 2006;
- Bhandari N, Sharma P, Taneja S, Kumar T, Rongsen-Chandola T, Appaiahgari MB, et al. A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial.
- Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, Sayinzoga-Makombe N, et al. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med [Internet]. 2017 Mar 23 [cited 2017 Jul 18];376(12):1121–30. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1609462
- Kulkarni P. Phase 3 efficacy study of a new pentavalent bovine-human reassortant rotavirus vaccine in India. In: 12th International Rotavirus Symposium. Melbourne; 2016. p. 28.
- John J, Kawade A, Rongsen-Chandola T, Bavdekar A, Bhandari N, Taneja S, et al. Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India. Vaccine. 2014;
