Efficacy, Immunogenicity, and Safety of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine at the End of Shelf Life

Abstract

BACKGROUND. Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide. Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies. OBJECTIVE. Our goal was to evaluate the efficacy, immunogenicity, and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants. PATIENTS AND METHODS. During 2002–2004, 1312 healthy infants ∼6 to 12 weeks old from the United States (47%) and Finland (53%) were randomly assigned to receive 3 oral doses of vaccine (vaccine at ∼1.1 × 107 infectious U per dose) or placebo ∼4 to 10 weeks apart. Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination. RESULTS. Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine (G1–G4). Efficacy against severe rotavirus gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent rotavirus vaccine recipients. No statistically significant increase in vomiting, diarrhea, or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose. A statistically significant increase in fevers (≥100.5°F, rectal equivalent) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1. CONCLUSIONS. This pentavalent human-bovine rotavirus vaccine was generally well tolerated, efficacious, and immunogenic at the end of shelf life.