Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

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In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus.

The most extensively explored strategy for rotavirus vaccination has been the Jennerian approach, which uses an antigenically related rotavirus strain from an animal host as the immunogen to induce protection against the 4 epidemiologically important group A rotavirus VP7 serotypes. Because this approach has shown limited efficacy, a modified Jennerian approach was developed with the goal of achieving broader antigenic coverage. Four VP7 serotypes were incorporated into a quadrivalent vaccine comprised of three rhesus-human rotavirus reassortants, each with 10 rhesus rotavirus genes and 1 human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity; the rhesus rotavirus itself provides coverage for VP7 serotype 3. This approach appears quite promising for preventing severe rotavirus diarrhea, including those episodes that lead to dehydration. Additional strategies under development stress the role not only of human rotavirus VP7 but also of human rotavirus VP4, the other outer capsid protein that also induces neutralizing antibodies.

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

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Rotavirus was a significant cause of medical visits at all three sentinel sites. Rotavirus caused less hospitalizations than previously reported in Argentina and Chile. On the basis of our findings we estimate that approximately 106,000/ 21,000, 48,000/8,000 and 98,000/31,000 rotavirus-associated medical visits/hospitalizations occur yearly in Argentina, Chile and Venezuela, respectively.

The genetic relatedness of 81 clinical rotavirus isolates to the human rotavirus prototype strains Wa (subgroup 2, serotype 1) and DS-1 (subgroup 1, serotype 2) was examined by RNA hybridization techniques. Labeled single-stranded (+) transcripts of Wa or DS-1 virus were incubated with denatured genomic rotaviral RNAs, and the resulting hybrids were subjected to gel electrophoresis and autoradiography. Nineteen of the specimens contained subgroup 1 rotavirus with a "short" RNA migration pattern. These viruses were found to be closely related to the DS-1 strain and were associated with illness of short duration. The remaining 62 isolates belonged to subgroup 2 and exhibited a "long" RNA migration pattern. Fifty-four of these isolates exhibited significant hybridization with the Wa strain probe. Four isolates yielded multiple hybrid bands with the Wa probe but also possessed at least one gene segment homologous to the DS-1 strain. The remaining four subgroup 2 rotaviruses did not exhibit significant homology in the form of labeled hybrid bands when tested with either the Wa or DS-1 probe. These findings suggest that most clinical rotavirus isolates belong to one of two human rotavirus "families" defined as Wa-like or DS-1-like. Our observations also suggest that reassortment occurs in vivo between rotaviruses belonging to the two human rotavirus "families" and that there are one or more additional families of human rotavirus.