A Phase 4, multicentre, randomized, single-blind clinical trial to evaluate the immunogenicity of the live, attenuated, oral rotavirus vaccine (116E), ROTAVAC®, administered simultaneously with or without the buffering agent in healthy infants in India

Abstract

Background: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration. Because ROTAVAC®, a WHO prequalified vaccine, was derived from the 116E neonatal strain, we evaluated the immunogenicity and safety of ROTAVAC® without buffer and ROTAVAC® with buffer in a phase 4, multicentre, single-blind, randomized clinical trial in healthy infants in India. Methods: 900 infants, approximately 6, 10 and 14 weeks of age, were assigned to 3 groups to receive ROTAVAC® (0.5 mL dose) orally: (i) 2.5 mL of citrate-bicarbonate buffer 5 minutes prior to administration of ROTAVAC® (Group I), (ii) ROTAVAC®, alone, without any buffer (Group II), or (iii) ROTAVAC®, mixed with buffer immediately before administration (Group III). Non–inferiority was compared among the groups for differences in serological responses (detected by serum anti-rotavirus IgA) and safety. Results: Geometric mean titers post vaccination at day 84 (28 days after dose 3) were 19.6 (95%CI: 17.0, 22.7), 20.7 (95%CI: 17.9, 24) and 19.2 (95%CI: 16.8, 22.1) for groups I, II and III respectively. Further, seroconversion rates and distribution of adverse events were similar among groups. Conclusions: Administration of ROTAVAC® at a 0.5 mL dose volume without buffering agent was shown to be well tolerated and immunogenic. Given the homologous nature of the strain, it is plausible that ROTAVAC® replicates well and confers immunity even without buffer administration.

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 Indian study of RotaTeq® showed 83% three-fold rise (seroconversion) in serum IgA antibodies, however the study did not include a placebo arm [19]. A recent study in India also showed seropositivity rates ranging from 38.3% (95%CI: 32.8, 43.9) to 42.1% (95%CI: 36.6, 47.9), with three different formulations of Rotavac [20].…”

Vaccine Safety and Efficacy in Preventing Rotavirus Infection

“…В связи с тем, что корреляционный показатель иммунной защиты до настоящего времени не установлен 18 [31,38], для живых ротавирусных вакцин изучали возможность использования других факторов иммунологического ответа (ASC-клеток, секретирующих антител и Т-клеток) [39,40]. Многие исследователи при оценке эффективности вакцины как альтернативу корреляционным показателям иммунной защиты рассматривают так называемые «лабораторные маркеры» эффективности иммунитета, например уменьшение количества ротавирусов, выделяемых с фекалиями, что является прямым отражением способности вакцины подавлять размножение вируса в кишечнике [41]. Увеличение концентрации эпидермального фактора роста (epidermal growth factor, EGF) в слюне может выступать в качестве лабораторного маркера эффективности иммунитета, так как РВИ связана с повышением экспрессии гена IFI27 в подчелюстных слюнных железах.…”

“…При проведении клинических исследований вакцин Rotavac ™ (Индия) и Rotаsiil ™ (Индия) в Индии и Африке повышение числа инвагинаций в группах иммунизированных детей по сравнению с числом инвагинаций в контрольных группах было незначительным [41,51,52]. Тем не менее польза от вакцинации против РВИ, благодаря профилактике развития тяжелой диареи и смертельного исхода в результате ротавирусного заболевания, намного превышает риск развития инвагинации кишечника 22 .…”

The 13th International Double-Stranded RNA Virus Symposium, Houffalize, Belgium, 24 to 28 September 2018

“…B. Benninghoff (GSK) and Esmée de Wolde (Merck) produced updates on the Rotarix and RotaTeq vaccines, respectively (64,66). Mithu Raychaudhuri (Bharat Biotech International) described the introduction of Rotavac in India in 2016 (67). Using CRISPR/Cas 9 methodology, Houping Wang (Centers for Disease Control and Prevention) described the production of Vero cells in which the WDR62 gene was knocked out and which permitted propagation of RVA vaccine strains to higher titers; the technology will require further exploration before it can be used for vaccine manufacturing (68).…”