Use of a Vaccinia Construct Expressing the Circumsporozoite Protein in the Analysis of Protective Immunity to Plasmodium yoelii

Antibodies to the circumsporozoite (CS) protein may play a role in the protective immunity induced by immunization with irradiated sporozoites. However, the observation that protection against a large (5000 sporozoites) inoculum is dependent on T cells of the suppressor/cytotoxic phenotype (CD8) has clearly established the importance of cellular mechanisms in this model system. In an attempt to stimulate a protective cellular immune response, Balb/CByJ mice were immunized intraperitoneally with one to 4 doses of a vaccinia recombinant construct expressing the entire CS protein of Plasmodium yoelii. The mice were challenged 2 weeks after the last dose of vaccine with 200 or 10,000 sporozoites. Mice vaccinated with irradiated sporozoites were protected, but all of the animals immunized with the recombinant construct became infected, even though tha anti-sporozoite IFA titers of both groups of vaccinated mice were comparable. To determine if the antibodies alone might be responsible for protecting mice immunized with irradiated sporozoites against a low dose challenge, we depleted them of CD8+ T cells, and found that they were no longer protected against even a 200 sporozoite challenge. It is unclear whether failure to protect mice with the vaccinia CS construct results from antigen presentation inadequate to induce the required cell mediated immune response, or whether the CS protein is not the appropriate antigen. Keywords: Malaria, Immunogens, Reprints. Pub. in Technological Advances in Vaccine Development: New Series, v84 p295-309 1988.