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

• Published in: Vaccine Vol. 17; no. 6; pp. 589 - 596
• Main Authors: Hanke, Tomáš, Neumann, Veronica C, Blanchard, Tom J, Sweeney, Paul, Hill, Adrian V.S, Smith, Geoffrey L, McMichael, Andrew
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 12.02.1999; Elsevier
• Subjects: AIDS Vaccines - immunology; AIDS/HIV; Animals; Biolistics; Biological and medical sciences; Combined vaccination; CTL polyepitope; Epitopes, T-Lymphocyte; Female; Fundamental and applied biological sciences. Psychology; Gene gun; HIV - immunology; Human immunodeficiency virus; Mice; Mice, Inbred BALB C; Microbiology; T-Lymphocytes, Cytotoxic - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Combined - immunology; Vaccines, DNA - immunology; Virology; Gene gun; CTL polyepitope; Combined vaccination; Protozoa; Apicomplexa; Microprojectile bombardment; Immune response; Antigenic determinant; Booster vaccination; Rodentia; Retroviridae; Intradermal administration; Recombinant DNA; Genetic vaccine; Polyvalent vaccine; Route of administration; Lentivirus; Intramuscular administration; Virus; Plasmodium falciparum; Vertebrata; Mammalia; Immunogenicity; Mouse; Human immunodeficiency virus
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(98)00238-2

Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the prime objectives of vaccine research. Previously, novel HIV vaccine candidates 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 Plasmodium falciparum: immunogenicity in mice. Vaccine 1998;16:426–435.] or modified vaccinia Ankara (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSC, Gilbert SG, Hill AVS, Smith GL, McMichael A. Immunogenicities of intravenous and intramuscular administrations of MVA-based multi-CTL epitope vaccine for HIV in mice. J Gen Virol 1998;79:83–90.]), i.e. vaccine vehicles 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 delivered intradermally using the Accell® gene gun. The CTL responses increased after re-immunization and after three deliveries were comparable to those induced by a single i.m. injection. Recent evidence indicates that combining routes and vaccine vehicles enhances the immunogenicity of vaccine-delivered 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 gun priming/i.m. boosting. A similar increment was obtained by sequential vaccinations using a gene gun-delivered DNA followed by recombinant MVA. Thus particular sequences of routes or vaccine vehicles rather than simple prime-boost delivery of a single vaccine is critical for an effective elicitation of CTL.