Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy |
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Authors: | Aidoo M; Lalvani A; Whittle HC; Hill AV; Robson KJ |
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Affiliation: | Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK. |
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Abstract: | Cytotoxic T lymphocytes (CTL) have been implicated in immunity to
Plasmodium falciparum infection and disease. We have previously described
the use of peptides to define malaria-specific CTL epitopes. To determine
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 protein (TRAP),
Pfs16 and the C- terminal half of liver-stage antigen (LSA)-1. Target cells
infected with recombinant viruses were lysed by malaria-specific CTL from
semi- immune African donors. We also tested the ability of cells infected
with these recombinant vaccinia viruses to re-stimulate malaria- specific
CTL in peripheral blood lymphocytes from malaria immune adults. Two other
pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a
canarypox virus, both expressing malaria antigens were also evaluated for
their ability to stimulate malaria-specific CTL in contrast to peptide,
none of these viruses successfully re- stimulated CTL from the peripheral
blood lymphocytes of semi-immune donors. The ability of human CTL from
naturally exposed individuals to recognize processed antigen supports the
relevance of these cells in protective immunity to malaria.
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