Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.
OBJECTIVE
Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs).


METHODS
In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus.


RESULTS
The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea.


CONCLUSIONS
RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis.
Rennels
M B
MB
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, USA.
Glass
R I
RI
Dennehy
P H
PH
Bernstein
D I
DI
Pichichero
M E
ME
Zito
E T
ET
Mack
M E
ME
Davidson
B L
BL
Kapikian
A Z
AZ
D000284:Administration, Oral; D004311:Double-Blind Method; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D012401:Rotavirus / Q000145:classification / Q000276:immunology*; D022243:Rotavirus Vaccines; D012703:Serotyping; D012720:Severity of Illness Index; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000627:therapeutic use*
D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; C052014:rhesus rotavirus vaccine