Rotavirus causes severe diarrhea in infants resulting in approximately 600,000 deaths worldwide and costing the United States 1.5 billion dollars annually. The only FDA-approved rotavirus vaccine was withdrawn in 1999 because of its association with intussusception. The subunit rotavirus vaccines that we are developing have been evaluated in a mouse model that measures rotavirus shedding as the endpoint for quantifying vaccine efficacies. Mucosal delivery of the vaccines has been found to elicit nearly complete protection against a subsequent oral rotavirus challenge. Because mice and humans are phylogenetically distant, it is necessary to establish a non-human primate model which will be used to validate the efficacy of our vaccine candidates using reduction of illness as the endpoint for measuring vaccine efficacies. In this proposal, the feasibility of a primate model for evaluating rotavirus vaccines is assessed by determining (1) the size of the """"""""window"""""""", in which young rhesus macaques are susceptible to developing diarrhea following rotavirus-induced illness and (3) whether titers of rotavirus-specific antibodies, and upregulated levels of cytokines in effector CD4+ and CD8+ lymphocytes correlate with protection. In a follow-up SBIR application, we will scale up and produce GMP-quality vaccines which will be used in safety and immunogenicity trials.
| McNeal, Monica M; Sestak, Karol; Choi, Anthony H-C et al. (2005) Development of a rotavirus-shedding model in rhesus macaques, using a homologous wild-type rotavirus of a new P genotype. J Virol 79:944-54 |
| Zhao, Wei; Xia, Mingjing; Bridges-Malveo, Tamika et al. (2005) Evaluation of rotavirus dsRNA load in specimens and body fluids from experimentally infected juvenile macaques by real-time PCR. Virology 341:248-56 |
| Sestak, K; McNeal, M M; Choi, A et al. (2004) Defining T-cell-mediated immune responses in rotavirus-infected juvenile rhesus macaques. J Virol 78:10258-64 |
