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

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.