title: Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy.
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.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK.
authors.forename: M
authors.initials: M
authors.lastname: Aidoo
authors.forename: A
authors.initials: A
authors.lastname: Lalvani
authors.forename: H C
authors.initials: HC
authors.lastname: Whittle
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
authors.forename: K J
authors.initials: KJ
authors.lastname: Robson
mesh_terms: D000328:Adult; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology / Q000821:virology; D010963:Plasmodium falciparum / Q000276:immunology*; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000469:parasitology* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte