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Efficient expansion of HIV-1-specific T cell responses by homologous immunization with recombinant Semliki Forest virus particles.

Sundbäck M, Douagi I, Dayaraj C, Forsell MN, Nordström EK, McInerney GM, Spångberg K, Tjäder L, Bonin E, Sundström M, Liljeström P, Karlsson Hedestam GB

Microbiology and Tumor Biology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Vaccines based on recombinant viruses represent a promising strategy for the development of a prophylactic vaccine against HIV-1. However, despite a proven capacity to stimulate potent HIV-1-specific immune responses, viral systems have limited utility in homologous prime-boost regimens due to the generation of anti-vector immune responses. It is therefore important to develop a diverse set of vaccine candidates that can be combined in different heterologous prime-boost regimens and/or to identify a vaccine candidate that is less sensitive to anti-vector mediated immunity. In this report, we describe the design and pre-clinical immunogenicity of a Semliki Forest virus-based vaccine, VREP-C, encoding Indian origin HIV-1 clade C antigens. We show that a single immunization with VREP-C stimulates HIV-1-specific IFNgamma ELISPOT responses, which were efficiently boosted by a second and a third homologous VREP-C immunization resulting in highly potent cytotoxic T cell responses. These results suggest that VREP-C may be a valuable component of a future prophylactic vaccine against HIV-1.

Published 11 October 2005 in Virology, 341(2): 190-202.
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