People living in areas where Plasmodium falciparum is endemic slowly develop immunity to malaria. Because immunity is achievable, it is likely a vaccine can be developed that will speed up the process. A vaccine against the erythrocyte state is of considerable importance because this is the stage that causes clinical disease, morbidity and mortality. Immunity to erythrocyte-stage asexual parasites is complex, but involves the participation of both Th1 and Th2 CD4 T cells which provide help for Ab production and cytokines for the activation of macrophages which release parasiticidal R0I and NO. Because T cells play a central role in asexual-stage immunity, additional information on T cell epitopes is needed before the development of a vaccine for malaria is an eventuality.

Over the last 4 years, the applicant has identified and characterized T cell epitopes from conserved regions of P. falciparim antigens that are known to contribute to immunity. The asexual-stage antigens include: ABRA, AMA-1, EBA, MSP-1, MSA-2, and SERA. Some T cell epitopes induce strong (immunodominant) responses, whereas, others are weaker (subdominant or cystic). Our current goal is to gain basic information about the immunogenicity of conserved T cell epitopes when they are combined and used as an immunogen. Specifically, our goals are to 1) find the best way to combine immunodominant, subdominant and cryptic T cell eptiopes such that they stimulate clonal expansion and the production of CD4+ memory cells for each of the antigens, ii) determine if the epitopes will be more immunogenic when formulated into polymers or multmeric peptides, and iii) confirm that human monocytes can process and present the polymers and multimers to sensited T cells. Results from the project should help establish guidelines for combining T cell epitopes into subunit vaccines. Such information will be relevant not only for malaria, but for other disease as well.

R21AI037943

1996-09-15

1999-03-14