A New Rotavirus Vaccine
A New Rotavirus Vaccine
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Chair, Department of Pediatrics; Director, Center for Pediatric Research, Eastern Virginia Medical School and Children's Hospital of the King's Daughter, is Associate Editor for Infectious Disease Alert.
Dr. Jenson is on the speaker's bureau for Merck.
Synopsis: In these 2 studies, the safety and efficacy of 2 new, different formulations of liquid oral rotavirus vaccines were studied in young infants. Both vaccines were highly efficacious in preventing rotavirus disease, especially severe disease. Neither vaccine was associated with an increased risk of intussusception or other severe adverse events. RotaTeq, one of the 2 vaccines studied, was approved by the FDA in February for young infants.
Sources: Ruiz-Palacios GM, et al. Safety and Efficacy of an Attenuated Vaccine Against Severe Rotavirus Gastroenteritis. N Engl J Med. 2006;354:11-22; Vesikari T, et al. Safety and Efficacy of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine. N Engl J Med. 2006;354:23-33.
Over 63,000 healthy infants from 11 latin american countries and Finland were randomized to receive either 2 oral doses of a live, attenuated human rotavirus vaccine or placebo at 2 and 4 months of age. The vaccine, developed by GlaxoSmithKline and planned to be marketed as Rotarix, contained 106.5 median cell-culture infective doses of the RIX4414 vaccine strain of G1P[8] specificity. Vaccination was 85% efficacious against severe rotavirus gastroenteritis and rotavirus-associated hospitalization (P < 0.001), and was almost 100% against the most severe disease. Hospitalization was reduced by 42% (95% CI, 29-53%; P < 0.001). Intussusception occurred in 6 vaccine recipients and 7 placebo recipients within 31 days.
Over 68,000 healthy infants 6-12 weeks of age from the United States and other countries were randomized to receive either 3 oral doses of live, pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-10 wk intervals in a blinded study. This vaccine was developed by Merck and licensed in February as RotaTeq. Vaccination reduced hospitalization and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring > 14 days after the third dose by 94.5% (95% CI, 91.2-96.6%). In the first full rotavirus season after vaccination, efficacy against severe rotavirus gastroenteritis was 98% (95.0% CI, 88.3-100%), and efficacy against any rotavirus gastroenteritis was 74.0% (95% CI, 66.8-79.9%). Clinic visits related to G1-G4 rotavirus gastroenteritis were reduced by 86.0% (95% CI, 73.9-92.5%). Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within 1 year after the first dose, including 6 vaccine recipients and 5 placebo recipients within 42 days of any dose (relative risk, 1.6; 95% CI, 0.4-6.4).
Commentary
Rotavirus is the leading cause of severe diarrhea-related illness and death in infants and young children in the United States and worldwide. Every year, rotavirus infection is associated with an estimated 55,000 hospitalizations in the United States and 2 million worldwide. Death from rotavirus is rare in the United States, but in developing countries, rotavirus gastroenteritis has been estimated to cause up to 600,000 deaths annually in children younger than 5 years of age. A safe, effective, and affordable vaccine is a priority for developing countries, where the disease burden is highest.
In 1998, a tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) was licensed as RotaShield and recommended for routine immunization of infants in the United States. It was withdrawn in October 1999 because of the association with intussusception, which occurred at an increased rate during the 3-14 days after the first dose and 3-7 days after the second dose. The attributable risk for intussusception with the RRV-TV rotavirus vaccine was estimated at approximately 1 per 10,000 vaccine recipients.
Each of these studies were designed and powered to evaluate the safety of these new vaccines with respect to intussusception by including a large sample size sufficient to detect intussusception at the rate that occurred with RRV-TV. Although neither of the new vaccines were associated with intussusception, the safety of the licensed vaccine will be monitored also in a post-licensure study of approximately 44,000 children. The Centers for Disease Control and Prevention (CDC) also evaluates vaccine safety in approximately 80,000 infants every year as part of the Vaccine Safety Datalink Program. In addition, the manufacturer is required to report cases of intussusception and all serious and unexpected adverse events to the FDA within 15 days of receiving notice, and to report all other adverse effects on a monthly basis.
The Advisory Committee on Immunization Practices (ACIP) has already recommended the vaccine for infants in a dosage regimen of 3 oral doses at 2, 4, and 6 months of age. The first dose should be administered by 12 weeks of age, with all 3 doses of vaccine by 32 weeks of age. These age guidelines reflect the design of the safety and efficacy study. There are insufficient data on safety and efficacy outside of these age ranges. The ACIP recommendations will become formal CDC recommendations as soon as they are published in the Morbidity and Mortality Weekly Report.
Over 63,000 healthy infants from 11 latin american countries and Finland were randomized to receive either 2 oral doses of a live, attenuated human rotavirus vaccine or placebo at 2 and 4 months of age.Subscribe Now for Access
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