No abstract

Primate rotavirus strain RRV and bovine strain WC3 or reassortants made between these animal viruses and human rotaviruses have been administered to infants as candidate vaccines. We compared RRV and WC3 in a murine model of oral infection. We determined the relative capacities of these viruses to induce a virus-specific humoral immune response by intestinal lymphocytes as tested by enzyme-linked immunospot assay, intestinal fragment culture, and enzyme-linked immunosorbent assay of intestinal contents. We found that inoculation of mice with RRV induced higher frequencies of virus-specific immunoglobulin A (IgA)-secreting cells in the lamina propria, greater quantities of virus-specific IgA in intestinal fragment cultures, and greater quantities of virus-specific IgA in intestinal secretions than did inoculation with WC3 or inactivated RRV (iRRV). The induction of an IgA response in serum was predictive of an IgA response among intestinal lymphocytes after inoculation with RRV but not WC3. In addition, large quantities of IgG, IgA, and IgM not specific for rotavirus were produced in fragment cultures from mice inoculated with RRV but not in cultures from mice inoculated with WC3 or iRRV. Possible mechanisms of RRV-induced polyclonal stimulation of intestinal B cells are discussed.

The capacity of an aqueous-based system of microencapsulation to enhance virus-specific humoral immune responses was evaluated in mice orally inoculated with noninfectious rotavirus (simian rotavirus strain RRV). Mice were orally inoculated with 1.75 or 0.35 microgram of inactivated RRV (iRRV) or microencapsulated iRRV. Sera, intestinal contents, and organ cultures of gut-associated lymphoid tissues (GALT) were tested for the presence of rotavirus-specific antibodies. Virus-specific IgA was produced by small intestine lamina propria lymphocytes in animals inoculated with 1.75 or 0.35 microgram of microencapsulated virus, but not in mice inoculated with unencapsulated virus. Virus-specific IgA in sera and intestinal contents were not predictive of intestinal organ culture responses. Microencapsulation may be an efficient way of inducing virus-specific immune responses in GALT after oral inoculation with small quantities of viral antigen. In addition, delayed release of virus from microcapsules may obviate the need for booster immunizations.