The objectives of the proposed investigation are: (1) to evaluate the role of the major outer capsid glycoprotein (p 38) of rotaviruses in evoking type-specific and crossreacting neutralizing antibodies, and (2) to assess the ability of those antibodies to protect against oral rotavirus challenge. We have recently developed a murine model for oral infection with heterologous rotaviruses; orally-infected adult and new born mice develop a type-specific immune response with the latter group also exhibiting symptoms of diarrhea and mild dehydration. Using this model we will assess the effect of the following active and passive modes of specific immunization on protection against challenge: (1) heterologous and homologous rotaviruses administered by different routes, (2) parenterally-administered viral subunit preparations, and (3) parenterally-administered antisera prepared against either whole virions or purified protein preparations. Monoclonal antibodies directed against the glycoprotein (p 38) will be generated in order to evaluate (a) the site(s) responsible for eliciting both type-specific and crossreactive viral neutralization, and (b) the effect of those antibodies when administered parenterally on protection against challenge.
