Vaccine Development Global Program

Non-replicating rotavirus vaccine development

Child laying on mother's chest.

The current available rotavirus vaccines mark a singular milestone in protecting children worldwide from this leading cause of severe, deadly diarrhea. PATH played an important role in clinical studies that showed these vaccines work in the most affected environments. But we discovered that, as with other oral, live vaccines, current rotavirus vaccines do not perform optimally in low-resource, high-burden settings of Africa and Asia, where 95 percent of rotavirus-related deaths occur. PATH is evaluating alternatives, investigating non-replicating vaccine candidates that do not contain live, attenuated rotavirus and are not administered orally.

Non-replicating rotavirus vaccine (NRRV) candidates offer a promising approach for improving protection through rotavirus vaccination for children at greatest risk. Current vaccines use attenuated—or weakened—live rotavirus to prompt the body’s immune system, but some studies have indicated the possibility of a very small increased risk of intussusception, a serious bowel disorder, after administration. Although the risk of intussusception is minimal and does not outweigh the benefit of immunization with live, oral rotavirus vaccines, NRRVs may remove this risk entirely. NRRVs also would be administered through routes other than the digestive tract, such as intramuscular injection. Administration through non-oral routes may overcome factors that can weaken an oral vaccine’s impact, such as high concentrations of maternal antibodies, compromised nutritional status, potential interference by other oral vaccines, and co-infections of the digestive system. In addition, NRRVs could potentially be included in a pediatric combination vaccine to simplify delivery.

PATH has identified the most promising NRRV candidates for fast-track development, and our activities encompass several stages along the vaccine development spectrum. We begin by working with manufacturing partners to refine formulations and finalize production processes. Once the candidates are ready for evaluation, we move them through preclinical testing to safety and immunogenicity studies, first in healthy adults and then in toddlers and infants. Results will pave the way for possible Phase 3 efficacy trials and, ultimately, an expanded market with new options for countries to consider as they plan for rotavirus vaccine introduction.

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