Effective induction of HIV-specific CTL by multi-epitope using gene gun ina combined vaccination regime

Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the prime objectives of vaccine research. Previously, novel HIV vaccine ca ndidates were constructed as a string of CTL epitopes (20 human, 3 macaque and 1 mouse) delivered using a DNA vector [Hanke T, Schneider J, Gilbert SG , Hill AVS, McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmod ium falciparum: immunogenicity in mice. Vaccine 1998;16:426-435.] or modifi ed vaccinia Ankara (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSG, Gilbert SG, Hill AVS, Smith GL, McMichael A. Immunogenicities of intravenous and intramuscular administrations of MVA-based multi-CTL epi tope vaccine for HIV in mice. J Gen Virol 1998;79:83-90.]), i.e. vaccine ve hicles acceptable for use in humans, In mice, a single intramuscular (i.m.) needle injection of either vaccine alone elicited good CTL responses. Here , it is demonstrated that the multi-epitope DNA also induced CTL when deliv ered intradermally using the Accell(R): gene gun. The CTL responses increas ed after re-immunization and after three deliveries were comparable to thos e induced by a single i.m. injection. Recent evidence indicates that combin ing routes and vaccine vehicles enhances the immunogenicity of vaccine-deli vered or -encoded antigens. Here, it is shown that administration of DNA by an i.m, priming/gene gun boosting more efficiently induced CTL than gene g un pr iming/i.m. boosting. A similar increment was obtained by sequential v accinations using a gene gun-delivered DNA followed by recombinant MVA. Thu s particular sequences of routes or vaccine vehicles rather than simple pri me-boost delivery of a single vaccine is critical for an effective elicitat ion of CTL. (C) 1999 Elsevier Science Ltd. All rights reserved.