Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine

Abstract

Background A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. Methods In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate – pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. Results A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. Conclusion BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

A Phase III open-label, randomized, active controlled clinical study to assess safety, immunogenicity and lot-to-lot consistency of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants

“…The secondary objectives were: To evaluate the safety of BRV-PV given concomitantly with UIP vaccines and to compare the immunogenicity of BRV-PV vaccine and Rotarix. The lot-to-lot consistency part of the study had an equivalence design while the non-interference with the UIP vaccines was assessed in non-inferiority design [15]. Immune response to Rotarix was also assessed in the study.…”

“…In addition, the serum samples were also tested for immune response to each of the EPI vaccines given concomitantly to evaluate any potential interference by BRV-PV. Results from those tests were published separately [15].…”

Profile: Vadu Health and Demographic Surveillance System Pune, India

“…VaduHDSS participation in conducting large community-based trials for meningitis, measles, typhoid, rotavirus and pneumococcal vaccines is one important contribution towards the development of safe, efficacious and affordable vaccines global use [15-20,22-25,28-30]. VaduHDSS has always led the technology portfolio within INDEPTH network and was instrumental in the development of online data repository iSHARE (www.INDEPTH-iSHARE.org).…”

Vaccine Safety and Efficacy in Preventing Rotavirus Infection

“…2018. https://drive.google.com/file/d/1tF0rhDmihpzd3B6BDFHcD8msDu1rqY jR/view 10 [21]. На основе штамма UK ротавируса крупного рогатого скота в Индии была разработана вакцина Rotasiil ® (Serum Institute of India), которая содержит реассортанты штаммов ротавируса человека и штамма ротавируса крупного рогатого скота, экспрессирующие антигены с типовой специфичностью G1, G2, G3, G4 и G9 [23,24].…”

“…По данным ВОЗ 24 , ротавирусные вакцины обладают благоприятным клиническим профилем безопасности и реактогенности, подобным профилю безопасности плацебо, и не увеличивают риск возникновения серьезных нежелательных реакций, включая риск инвагинации. Вместе с тем, низкий уровень достоверности не позволяет полностью исключить риски возникновения инвагинации при применении указанных вакцин [51].…”