Vaccine Development Global Program

Evaluation of current rotavirus vaccines

Infant receives oral rotavirus vaccine in Nicaragua.

Photo: PATH/Mike Wang.

Rotavirus—the leading cause of severe childhood diarrhea—accounts for approximately one-third of all child deaths from diarrhea worldwide. In countries where new rotavirus vaccines have been broadly introduced—mostly high- and middle-income countries of the Americas—vaccination is dramatically reducing hospitalizations and deaths.

Still, the overwhelming majority of rotavirus deaths occur in developing countries of Africa and Asia, making studying the potential impact of these live, oral rotavirus vaccines essential for prompt introduction. Between 2005 and 2009, PATH led such evaluations and found that Rotarix® (GlaxoSmithKline) and Rotateq® (Merck & Co., Inc.) demonstrated significant efficacy among high-burden, low-income populations. But efficacy was lower than that seen in high- and middle-income countries. Building off these pivotal findings, we are now studying approaches to improve rotavirus vaccine performance and ensure greatest impact.

Reasons for the lower efficacy of live, oral vaccines in various settings may include host factors (such as maternal antibody levels, age of vaccination, malnutrition, concomitant intestinal infections, or infestation), vaccine factors (such as vaccine dose or number of doses), or virus factors (such as lack of protection against particular strains). We’re conducting studies in Africa and Asia to better understand the roles of these factors and, ultimately, evolve immunization strategies to enhance immune response and efficacy.

Maternal antibodies are higher in younger infants, and their presence may result in a lower immune response to rotavirus vaccination. We’re investigating whether initiating vaccination at a slightly later age, when these antibodies have waned, or providing an additional dose of vaccine can increase efficacy. Booster doses may also help sustain initial levels of protection through the second year of life. An optimal timing for an additional dose of rotavirus vaccine would be at the time of a child’s first measles vaccination. Thus, we’re also evaluating the coadministration of rotavirus and measles vaccines. These studies will test the Rotarix® vaccine, providing an additional third dose beyond the recommended two doses to determine a potential beneficial effect.

Additional studies will focus on the promising potential of zinc and probiotics provided at the time of rotavirus vaccination to overcome and enhance limited immune responses to the oral vaccines. We also plan to reveal the role of different strains on vaccine efficacy and the clinical protection that rotavirus vaccines confer against individual strains.

Even at lower efficacy in countries that carry the greatest burden, rotavirus vaccines will substantially reduce severe cases and deaths. Particularly in Africa and Asia, they have the potential to make a huge impact. Combined with our efforts to study new rotavirus vaccine candidates and support countries considering introduction of the current vaccines, our research into improving efficacy in high-burden areas rounds out a comprehensive approach that will ensure rotavirus vaccines realize their tremendous potential.

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