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The desirability of inducing cytotoxic T cell responses to defined epitopes in humans has led to the development of a variety of recombinant delivery systems. Recombinant protein particles derived from a yeast retrotransposon (Ty) and the modified Ankara vaccinia (MVA) virus can deliver large epitope strings or even whole proteins. Both have previously been administered safely in humans. Immunization with recombinant Ty and MVA containing a single Plasmodium berghei class I-binding epitope provided 95% sterile protection against malaria in mice. The sequence of immunization, Ty followed by MVA, was critical to elicit high levels of IFN-gamma-producing cells and protection. The reciprocal sequence (MVA/TY) or homologous boosting was not protective. Both constructs (Ty and MVA) contain the H-2Kd-restricted pb9 CTL epitope from the circumsporozoite protein of P. berghei among a string of 8-15 human P. falciparum-derived CTL epitopes restricted through 7 common HLA alleles as well as widely recognized CD4 T cell epitopes. Thus, the novel recombinant Ty/MVA prime/boost combination with these constructs provides a safe alternative for evaluation for human vaccination against P. falciparum malaria.

Original publication

DOI

10.1002/(SICI)1521-4141(199812)28:12<4345::AID-IMMU4345>3.0.CO;2-P

Type

Journal article

Journal

Eur J Immunol

Publication Date

12/1998

Volume

28

Pages

4345 - 4355

Keywords

Animals, Antigens, Protozoan, Cytotoxicity, Immunologic, Drug Delivery Systems, Histocompatibility Antigens Class I, Humans, Malaria, Malaria Vaccines, Mice, Plasmodium berghei, Recombinant Proteins, T-Lymphocytes