Using recent advances in biological and medical sciences, a new candidate human immunodeficiency virus (HIV) vaccine has been developed and tailor-designed for a phase III clinical trial in Kenya. It has two components, DNA and MVA (an attenuated poxvirus), used in a prime-boost vaccination protocol. Both of these vaccine vehicles express a common ‘chimeric’ protein derived from small parts of the HIV genome. The vaccine focuses on the induction of cell-mediated immune responses.
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McMichael, A.J. & Hanke, T. Is an HIV vaccine possible? Nature Med. 5, 612– 614 (1999).
Wyatt, R. et al. The antigenic structure of the HIV gp120 envelope glycoprotein . Nature 393, 705–711 (1998).
Kolchinsky, P. et al. Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication. J. Virol. 73, 8120–8126 ( 1999).
Binley, J.M. et al. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J. Virol. 74, 627– 643 (2000).
Yang, O.O. et al. Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms. J. Virol. 71, 3120–3128 (1997).
Wagner, E. et al. Beta-chemokines are released from HIV-1-specific cytolytic T cell granules complexed to proteoglycans. Nature 391 , 908–911 (1998).
Price, D.A. et al. Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. Curr. Biol. 8, 355–358 (1998).
Rowland-Jones, S.L. et al. HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nature Med. 1, 59– 64 (1995).
Rowland-Jones, S.L. et al. Cytotoxic T cell responses to multiple conserved epitopes in HIV-resistant prostitutes in Nairobi. J. Clin. Inv. 102, 1758–1765 (1998).
Rowland-Jones, S.L. et al. HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. Lancet 341, 860– 861 (1993).
Pinto, L.A. et al. Env-specific cytotoxic T lymphocytes in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. J. Clin. Invest. 96, 867–876 (1995).
Gallimore, A. et al. Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated animals. Nature Med. 1, 1167–1173 (1995).
Cafaro, A. et al. Control of SHIV-89.6P infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nature Med. 5, 643– 650 (1999).
McMichael, A. T cell responses and viral escape. Cell 93, 673–676 (1998).
Ridge, J.P., Di Rosa, F. & Matzinger, P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393, 474–478 (1998).
Rosenberg, E.S. et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447– 1450 (1997).
Kalams, S.A. et al. Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection. J. Virol. 73, 6715–6720 (1999).
Clerici, M. et al. HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood. JAMA 271, 42–46 (1994).
Kaul, R. et al. HIV-1 specific mucosal IgA in a cohort of HIV-1 resistant Kenyan sex workers. AIDS 13, 23– 29 (1999).
Ferrari, G. et al. Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc. Natl. Acad. Sci. USA 94, 1396–1401 (1997).
Gahery-Segard, H. et al. Multiepitopic B- and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine. J. Virol. 74, 1694–1703 ( 2000).
Hanke, T., Schneider, J., Gilbert, S.C., Hill, A.V.S. & McMichael, A. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: Immunogenicity in mice. Vaccine 16, 426–435 ( 1998).
Hanke, T. et al. Immunogenicities of intravenous and intramuscular administrations of MVA-based multi-CTL epitope vaccine for HIV in mice. J. Gen. Virol. 79, 83–90 ( 1998).
Hanke, T. & McMichael, A. Pre-clinical development of a multi-CTL epitope-based DNA prime-MVA boost vaccine for AIDS. Immunol. Lett. 66, 177–181 (1999).
Hanke, T. et al. Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine 16, 439–445 ( 1998).
Schneider, J. et al. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nature Med. 4, 397–402 (1998).
Hanke, T. et al. Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. J. Virol. 73, 7524–7532 (1999).
Allen, T.M. et al. Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. J. Immunol. 164 , 4968–4978 (2000).
Neilson, J.R. et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya. J. Virol. 73, 4393–4403 (1999).
Whitton, J.L., Sheng, N., Oldstone, M.B. & McKee, T.A. A “string-of-beads” vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge. J. Virol. 67, 348–352 (1993).
Thomson, S.A. et al. Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design. Proc. Natl. Acad. Sci. USA 92, 5845 –5849 (1995).
Thomson, S.A. et al. Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J. Immunol. 160, 1717– 1723 (1998).
Hanke, T. et al. Effective induction of HIV-specific CTL by multi-epitope DNA using a gene gun in a combined vaccination regime. Vaccine 17, 589–596 (1999).
Dorrell, L. et al. Distinct recognition of clade A HIV-1 epitopes by cytotoxic T lymphocytes generated from donors infected in Africa. J. Virol. 73, 1708–1714 ( 1999).
Whittle, N. et al. Expression in COS cells of a mouse-human chimeric B72.3 antibody . Protein Eng. 1, 499–505 (1987).
Williams, S.G. et al. Repressor titration: a novel system for selection and stable maintenance of recombinant plasmids. Nucleic Acids Res. 26, 2120–2124 (1998).
Mayr, A., Hochstein-Mintzel, V. & Stickl, H. Abstammung, Eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA. Infection 105, 6– 14 (1975).
Moss, B. et al. Host range restricted, non-replicating vaccinia virus vectors as vaccine candidates. Adv. Exp. Med. Biol. 397, 7–13 (1996).
Seth, A. et al. Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer. Proc. Natl. Acad. Sci. USA 95, 10112–10116 (1998).
Tough, D.F., Borrow, P. & Sprent, J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947–1950. (1996).
Blanchard, T.J., Alcami, A., Andrea, P. & Smith, G.L. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J. Gen. Virol. 79, 1159–1167 (1998).
Takahashi, H., Nakagawa, Y., Yokomuro, K. & Berzofsky, J.A. Induction of CD8+ cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells. Int. Immunol. 5, 849–857 ( 1993).
Betts, M.R. et al. Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians. J. Virol. 71, 8908–8911 (1997).
Ogg, G.S. et al. Four novel cytotoxic T-lymphocyte epitopes in the highly conserved major homology region of HIV-1 Gag, restricted through B*4402, B*1801, A*2601, B*70. AIDS 12, 1561–1563 ( 1998).
Rowland-Jones, S.L. et al. Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly-exposed persistently seronegative donors. Immunol. Lett. 66, 9–14 (1999 ).
The authors thank Roshni Dasgupta, Sarah Rowland-Jones, Eric Prieur and Rocky Cranenburgh for advice and help. Grant supports from the Medical Research Council (MRC) UK and the International AIDS Vaccine Initiative are fully acknowledged.
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