RECOMBINANT VACCINIA VIRUSES FOR THE CHARACTERIZATION OF PLASMODIUM FALCIPARUM-SPECIFIC CYTOTOXIC T-LYMPHOCYTES - RECOGNITION OF PROCESSED ANTIGEN DESPITE LIMITED RE-STIMULATION EFFICACY

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plas modium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determ ine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive pr otein (TRAP), Pfs16 and the C-terminal half of liver-stage antigen (LS A)-1. Target cells infected with recombinant viruses were lysed by mal aria-specific CTL from semi-immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to r e-stimulate malaria-specific CTL in peripheral blood lymphocytes from malaria immune adults, Two other pox virus recombinants, NYVAC, an att enuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate ma laria-specific CTL. In contrast to peptide, none of these Viruses succ essfully re-stimulated CTL from the peripheral blood lymphocytes of se mi-immune donors, The ability of human CTL from naturally exposed indi viduals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria.