Research Project
3506008
Peptide carrier and recombinant DNA produced Plasmodium falciparum sporozoite subunit vaccines are being tested in clinical trials. These vaccines are designed to induce high titer protective antisporozoite antibodies. Efficacy of these vaccines is partial at best. Recent studies compared analogous peptide and recombinant subunit vaccines with sporozoite induced immunity in the P. berghei model. These studies showed that parenterally administered P. berghei subunit vaccines induce high titer sporozoite antibody which is partially protective at low sporozoite challenge doses. In contrast, sporozoite induced immunity, fully protect at 20 times the challenge, is mediated by cellular immunity. These studies are designed to examine the feasibility of immunizing mice against P. berghei sporozoites, a rodent malaria parasite, by oral vaccination. Vaccination of mice with an attenuated Salmonella strain harboring plasmids which express the CS protein as expected to elicit not only antibody but also cell mediated immune responses. The P. berghei CS gene will be fused to the gene encoding the B subunit of the heat labile enterotoxin of E. coli (LTB) at various locations and the fusion protein tested for immunogenicity. One set of constructions, fusing the first 30 amino acids of LT-B with gene fragments of the P. berghei C5 gene, has been expressed and is currently being tested for immunogenicity, preliminary results are presented. If these studIes are successful, analogous oral malaria vaccines could be developed for humans.
