Rotavirus vaccines: an overview

Abstract

Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

FIG. 1.

Seasonal trends in rotavirus activity in the United States from September 2005 through September 2007. These data are from the National Respiratory and Enteric Virus Surveillance System, a voluntary, laboratory-based system organized by the CDC, Atlanta, GA. The National Respiratory and Enteric Virus Surveillance System prospectively monitors seasonal trends in viral activity on a weekly basis.

FIG. 2.

Schematic representation of a rotavirus virion. The virus is composed of three protein shells, an outer capsid, an inner capsid, and an internal core, that surround the 11 segments of double-stranded RNA. The outer capsid proteins VP4 and VP7 are neutralization antigens and define the P and G serotypes, respectively. VP6, the inner capsid structural protein, is the subgroup antigen. (Reprinted from reference by permission from Macmillan Publishers.)

FIG. 3.

Distribution of rotavirus serotypes worldwide and in the United States. (A) Global distribution from 1989 to 2004. The G serotypes of >88% of rotavirus strains worldwide are G1, G2, G3, and G4. The P serotype of >80% of rotavirus strains worldwide is P1A[8]. (B) U.S. distribution from 1973 to 2003. The G serotypes of >97% of rotavirus strains in the United States are G1, G2, G3, and G4. The P serotype of >80% of rotavirus strains is P1A[8]. This figure is based on data from reference .

FIG. 4.

Interval between vaccination with RRV-TV and the development of intussusception. (Reprinted from reference with permission, copyright ©2007 Massachusetts Medical Society.)

FIG. 5.

Human-bovine rotavirus reassortant vaccine (RotaTeq). This vaccine contains five reassortant rotaviruses. Four reassortant rotaviruses express the VP7 protein (G1, G2, G3, or G4) from the human rotavirus parent strain and the VP4 protein (P7[5]) from the bovine rotavirus parent strain. The fifth reassortant virus expresses the VP4 protein (P1A[8]) from the human rotavirus parent strain and the outer capsid protein G6 from the bovine rotavirus parent strain. (Adapted with permission from SLACK Inc. [62a].)