Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial.
BACKGROUND
Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89-12, in US children in a randomised, placebo-controlled, double-blind multicentre trial.


METHODS
215 healthy infants were enrolled, of whom 213 were given two doses of 89-12 (containing 1x10(5) plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89-12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis.


RESULTS
Adverse reactions were mild. Low-grade fever (> or = 38.1 degrees C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0.001). An immune response to vaccine was detected in 94.4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89.0% [95% CI 65.4-94.5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care.


CONCLUSIONS
The 89-12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings.
Bernstein
D I
DI
Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. dib@chmcc.org
Sack
D A
DA
Rothstein
E
E
Reisinger
K
K
Smith
V E
VE
O'Sullivan
D
D
Spriggs
D R
DR
Ward
R L
RL
D000284:Administration, Oral; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000175:diagnosis / Q000517:prevention & control; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; C113153:rotavirus vaccine 89-12