The pentavalent rotavirus vaccine, RotaTeq

Vaccination against rotavirus disease has been a global preventive health priority since rotaviruses were first discovered in the 1970s. The first licensed rotavirus vaccine, RRV-TV, was removed from the market shortly after licensure because of an unexpected serious adverse event, intussusception. A pentavalent rotavirus vaccine, PRV, is the second FDA-licensed rotavirus vaccine and does not signal the risk observed with RRV-TV. The properties and large safety study results of PRV are reviewed here.     

The new pentavalent rotavirus vaccine composed of bovine (strain WC3) -human rotavirus reassortants

BACKGROUND: Infantile gastroenteritis caused by human rotaviruses is a prevalent disease throughout the world, causing dehydration and hospitalization in all countries. In developing countries, it is associated with a high mortality. A licensed vaccine against rotavirus was withdrawn because of a causal association with intussusception. A new vaccine has been developed and is a candidate for licensure. METHODS: To recount the early development and recent demonstration of the safety and efficacy of the new vaccine. A bovine rotavirus attenuated for humans was isolated and reassorted with human rotaviruses of serotypes G1-4 and P1 to create a pentavalent vaccine. Multiple placebo-controlled clinical trials, including one involving approximately 70,000 infants, were conducted in multiple developed countries. RESULTS: The pentavalent vaccine was well tolerated by infants less than 8 months of age, and the incidence of intussusception was similar among vaccine and placebo recipients. More than 90% of infants had a significant rise in serum antirotavirus IgA titer after 3 doses. Efficacy of 95% against severe disease causing hospitalization or emergency care was demonstrated, and pentavalent vaccine prevented 74% of all rotavirus disease. CONCLUSIONS: If widely used, pentavalent vaccine would control rotavirus disease in the United States and other developed countries and could also have a major effect in developing countries.     

Population-based study of rotavirus vaccination and intussusception

BACKGROUND: During the first year that the rhesus rotavirus tetravalent vaccine (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received several reports of intussusception after vaccination. To evaluate the risk of intussusception, we conducted a retrospective cohort study in ten managed care organizations. METHODS: Cases of intussusception were identified by searching electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in infants 1 to 11 months of age and confirmed by medical chart review. Vaccination and enrollment data were obtained from administrative databases. Incidence rate ratios (RR) of intussusception were computed by dividing incidence rates in prespecified risk intervals after vaccination by the background rate of intussusception and adjusted for age by Poisson regression. Cox proportional hazard regression was used to evaluate risk by vaccine dose. RESULTS: Of 463,277 children 56,253 had been vaccinated with a total of 91 371 doses of RRV-TV. The incidence rate of intussusception was 25/100,000 person years among unexposed infants and 340/100,000 person years 3 to 7 days postvaccination. In the interval 3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval, 8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk intervals were >1.0, but the confidence intervals substantially overlapped 1.0. The attributable risk was one case of intussusception per 11 073 children vaccinated. CONCLUSIONS: RRV-TV is associated with an increased risk of intussusception. The risk is greatest 3 to 7 days after the first vaccination dose.     

Duration and pattern of asymptomatic rotavirus shedding by hospitalized children

Fecal shedding of rotaviruses by infants and children without gastrointestinal symptoms has recently been recognized, but little is known about the duration or frequency of virus shedding in such patients. We therefore evaluated rotavirus shedding by 16 infants and children during the course of their prolonged hospitalizations. Repeated fecal specimens were obtained from these patients and examined for the presence of rotavirus by means of immunoassay, electron microscopy and polyacrylamide gel electrophoresis. Asymptomatic rotavirus shedding was observed in each of the 16 patients, and more than 1 episode of virus excretion was detected in 15 of these. Electropherotype analysis indicated that some of these episodes were probably the result of reinfection with different strains of rotavirus. Asymptomatic shedding may be important in transmission of rotaviruses. Its role should be taken into consideration in future investigations of the epidemiology and control of this nosocomial pathogen.     

The role of the rotavirus vaccine in childhood vaccination schedules

Rotavirus is the leading cause of diarrhea in infants. In developed countries, this infection leads to considerable morbidity with a high number of hospitalizations and medical interventions in the winter season, giving rise to substantial medical and social costs. In developing countries, rotavirus is a major cause of mortality in infants due to dehydration, with an estimated 600.000 deaths or more per year worldwide. A vaccine that is easy administrated, safe and with high efficacy would be the ideal means to reduce the burden of this disease and its high economic and social cost and to decrease the number of deaths in low-income countries. Recently, the results of two well-designed clinical trials with a large number of subjects have been reported. Both studies, which used different vaccines, reported high efficacy in the prevention of severe gastroenteritis and hospitalizations caused by rotavirus. When these vaccines become available in Europe, a reduction in hospitalizations, medical consultations, and days of work lost can be expected.     

Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report

We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis.     

Efficacy of pentavalent human-bovine (WC3) reassortant rotavirus vaccine based on breastfeeding frequency

The efficacy of a live, oral, pentavalent rotavirus vaccine against G1-4 rotavirus gastroenteritis (RVGE) was retrospectively assessed based on breastfeeding frequency among 5098 infants in a placebo-controlled trial. The efficacy against any RVGE severity for infants never breastfed, sometimes breastfed, or exclusively breastfed was 68.3%, 82.2%, and 68.0%, respectively. The efficacy against severe RVGE was 100%, 95.4%, and 100%, respectively. Breastfeeding did not seem to adversely impact the efficacy of pentavalent rotavirus vaccine.