A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees

Two chimpanzees were vaccinated intramuscularly against malaria using plasm id DNA expressing the pre-erythrocytic antigens thrombospondin related adhe sion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasm odium falciparum together with GM-CSF protein. A recombinant modified vacci nia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 wee ks later to boost the immune response. This sequence of antigen delivery in duced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected afte r four DNA injections, and were boosted by injection of recombinant MVA exp ressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were de tected in both animals, but only after boosting with recombinant MVA. By sc reening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied . T cells specific for this epitope were present in PBMCs and liver-infiltr ating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection again st P. falciparum malaria in humans. (C) 2001 Elsevier Science Ltd. All righ ts reserved.