Protection from Plasmodium berghei infection by priming and boosting T cells to a single class I-restricted epitope with recombinant carriers suitable for human use

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 epitop e strings or even whole proteins. Both have previously been administered sa fely in humans. Immunization with recombinant Ty and MVA containing a singl e Plasmodium berghei class 1-binding epitope provided 95 % sterile protecti on against malaria in mice. The sequence of immunization, Ty followed by MV A, was critical to elicit high levels of IFN-gamma-producing cells and prot ection. The reciprocal sequence (MVA/TY) or homologous boosting was not pro tective. Both constructs (Ty and MVA) contain the H-2K(d)-restricted pb9 CT L 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 nov el recombinant Ty/MVA prime/boost combination with these constructs provide s a safe alternative for evaluation for human vaccination against P. falcip arum malaria.