Rotavirus vaccines for global use: What are the remaining issues and challenges?

*Correspondence to: Baoming Jiang; Email: bxj4@cdc.gov In June 2009, the Strategic Advisory Group of Experts (SAGE) of the World Health Organization (WHO) issued a recommendation for global use of the two currently licensed live oral rotavirus vaccines, a pentavalent human-bovine reassortant RotaTeq developed by Merck and a monovalent attenuated human strain RotarixTM from GlaxoSmithKline. This represented an expansion of an initial SAGE recommendation in 2007 that vaccines be used in the Americas and Europe where vaccine efficacy had been established in pivotal pre-licensure trials. The expansion was based, in large part, on efficacy data from recently completed clinical trials that established the efficacy of RotarixTM in Malawi and South Africa and effectiveness results from postlicensure studies of the two vaccines in El Salvador and Nicaragua. The global recommendation for rotavirus vaccination is welcome news for millions of young children throughout the world. Each year, rotavirus is estimated to cause more than 125 million diarrhea illnesses, 24 million outpatient visits, 2 million hospitalizations, and approximately 527,000 deaths in children <5 years of age worldwide, with >85% of rotavirus deaths occurring in the low income countries of sub-Saharan Africa and Asia. Vaccination is thus likely to substantially reduce severe morbidity and mortality from rotavirus; early data from high and middle income countries in the Americas and Australia that have been using rotavirus vaccines in their routine immunization schedules for the past 2–3 years are quite encouraging. For example, in both the United States and Australia, the introduction of rotavirus vaccines has resulted in a dramatic decline in cases of rotavirus diarrhea, including possible indirect benefits of vaccination (i.e., herd immunity) leading to disease reduction in older unvaccinated children. Despite this early success, some issues and challenges remain and need to be addressed. First, data from recently completed clinical trials and post-licensure studies indicate that both vaccines are significantly less immunogenic and effective in low-income countries of Africa, Asia and Latin America where a highly effective vaccine is needed most. For example, the immunogenicity of RotarixTM ranged from >90% in Finland to ∼60% in Latin America and 40% to 50% in low-income countries of Africa and Asia. Similarly, efficacy of RotarixTM against severe rotavirus disease ranged from >90% in Europe to 85% in Latin America to 76% in South Africa and only 49% in Malawi. Clinical trials of RotaTeq recently completed in Africa and Asia have yielded similar results. Thus, the gradient in immune response and protective efficacy appears to be directly related to the socio-economic status of the population. These findings are not unexpected because live oral rotavirus vaccines previously tested in the 1980s and 1990s were also less effective in developing countries and other live oral vaccines against polio (OPV) and cholera have also shown diminished performance in resource-limited settings. While even a moderately effective rotavirus vaccine will have a substantial impact in developing country settings with high disease burden, room for improving vaccine performance remains. Rotavirus vaccines for global use