Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine
Timo Vesikari, M.D., David O. Matson, M.D., Ph.D., Penelope Dennehy, M.D., Pierre Van Damme, M.D., Ph.D., Mathuram Santosham, M.D., M.P.H., Zoe Rodriguez, M.D., Michael J. Dallas, Ph.D., Joseph F. Heyse, Ph.D., Michelle G. Goveia, M.D., M.P.H., Steven B. Black, M.D., Henry R. Shinefield, M.D., Celia D.C. Christie, M.D., M.P.H., Samuli Ylitalo, M.D., Robbin F. Itzler, Ph.D., Michele L. Coia, B.A., Matthew T. Onorato, B.S., Ben A. Adeyi, M.P.H., Gary S. Marshall, M.D., Leif Gothefors, M.D., Dirk Campens, M.D., Aino Karvonen, M.D., James P. Watt, M.D., M.P.H., Katherine L. O'Brien, M.D., M.P.H., Mark J. DiNubile, M.D., H Fred Clark, D.V.M., Ph.D., John W. Boslego, M.D., Paul A. Offit, M.D., Penny M. Heaton, M.D., for the Rotavirus Efficacy and Safety Trial (REST) Study Team
Background Rotavirus is a leading cause of childhood gastroenteritisand death worldwide.
Methods We studied healthy infants approximately 6 to 12 weeksold who were randomly assigned to receive three oral doses oflive pentavalent human–bovine (WC3 strain) reassortantrotavirus vaccine containing human serotypes G1, G2, G3, G4,and P[8] or placebo at 4-to-10-week intervals in a blinded fashion.Active surveillance was used to identify subjects with seriousadverse and other events.
Results The 34,035 infants in the vaccine group and 34,003 inthe placebo group were monitored for serious adverse events.Intussusception occurred in 12 vaccine recipients and 15 placeborecipients within one year after the first dose including sixvaccine recipients and five placebo recipients within 42 daysafter any dose (relative risk, 1.6; 95 percent confidence interval,0.4 to 6.4). The vaccine reduced hospitalizations and emergencydepartment visits related to G1–G4 rotavirus gastroenteritisoccurring 14 or more days after the third dose by 94.5 percent(95 percent confidence interval, 91.2 to 96.6 percent). In anested substudy, efficacy against any G1–G4 rotavirusgastroenteritis through the first full rotavirus season aftervaccination was 74.0 percent (95 percent confidence interval,66.8 to 79.9 percent); efficacy against severe gastroenteritiswas 98.0 percent (95 percent confidence interval, 88.3 to 100percent). The vaccine reduced clinic visits for G1–G4rotavirus gastroenteritis by 86.0 percent (95 percent confidenceinterval, 73.9 to 92.5 percent).
Conclusions This vaccine was efficacious in preventing rotavirusgastroenteritis, decreasing severe disease and health care contacts.The risk of intussusception was similar in vaccine and placeborecipients. (ClinicalTrials.gov number, NCT00090233
[ClinicalTrials.gov]
.)
Source Information
From the University of Tampere Medical School, Tampere, Finland (T.V., S.Y., A.K.); the Center for Pediatric Research, Eastern Virginia Medical School, Norfolk (D.O.M.); the Division of Pediatric Infectious Diseases, Rhode Island Hospital, Providence (P.D.); the Center for the Evaluation of Vaccination, University of Antwerp, Antwerp, Belgium (P.V.D.); the Center for American Indian Health, Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore (M.S., J.P.W., K.L.O.); the University of Puerto Rico School of Medicine, San Juan (Z.R.); Merck Research Laboratories, West Point, Pa. (M.J. Dallas, J.F.H., M.G.G., R.F.I., M.L.C., M.T.O., B.A.A., M.J. DiNubile, J.W.B., P.M.H.); Kaiser Permanente Vaccine Study Center, Oakland, Calif. (S.B.B.); the Institute of Vaccine and Pharmacologic Research in San Francisco, San Francisco (H.R.S.); the Department of Pediatrics, University of the West Indies, Kingston, Jamaica (C.D.C.C.); the Department of Pediatrics, University of Louisville School of Medicine, Louisville, Ky. (G.S.M.); the Department of Clinical Sciences Pediatrics, Umea University, Umea, Sweden (L.G.); Sanofi Pasteur Merck, Sharp & Dohme, Lyon, France (D.C.); and Children's Hospital and the University of Pennsylvania School of Medicine, Philadelphia (HF.C., P.A.O.).
Address reprint requests to Dr. Heaton at Merck Research Laboratories, P.O. Box 4, UNC-151, West Point, PA 19486, or at penny_heaton{at}merck.com.
Rotavirus Vaccines
Molinaro G. A., Lee D. A., Lee P.-I., Simonsen L., Taylor R. J., Kapikian A. Z., Ruiz L. P. Jr., O'Ryan M., Ruiz-Palacios G. M., Clemens R., Vesikari T., DiNubile M. J., Heaton P. M., Glass R. I., Parashar U. D.
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N Engl J Med 2006;
354:1747-1751, Apr 20, 2006.
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