Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation

BACKGROUND.A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine. OBJECTIVE.We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate. METHODS.During 1997 through 1998, 731 healthy infants ∼2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses ∼6 to 8 weeks apart in a partially double blinded study. Infants were randomized to(1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo. RESULTS.No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (≥38.1°C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a ≥3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group. CONCLUSIONS.HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.