Louis Miller (National Institute of Allergy and Infectious Diseases) and Stephen Hoffman (Naval Medical Research Institute) review progress toward developing malaria vaccines. They argue that multiple antigens from different stages may be needed to protect the diverse populations at risk, and that an optimal vaccine would induce immunity against all stages. Vaccines for African children, in whom the major mortality occurs, must induce immunity against asexual blood stages.
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References
Miller, L.H., Good, M.F. & Milon, G. Malaria pathogenesis. Science 264, 1878–1883 (1994).
Marsh, K. Malaria—a neglected disease? Parasitology 104, S53–S69 (1992).
Snow, R.W. et al. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet 349, 1650–1654 (1997).
Hoffman, S.L. (ed.) Malaria Vaccine Development: A Multi-Immune Response Approach. Washington, D.C.: ASM Press (1996).
Good, M.F., Kaslow, D.C. & Miller, L.H. Pathways and strategies for developing a malaria blood stage vaccine. Ann. Rev. Immunol. 16, 57–87 (1998).
Hoffman, S.L., Franke, E.D., Hollingdale, M.R. & Druilhe, P. Attacking the infected hepatocyte. In: Malaria Vaccine Development: A Multi-Immune Response Approach, Hoffman, S.L. (ed.) Washington, D.C: American Society of Microbiology, pp. 35–75 (1996).
Doolan, D.L. et al. Degenerate cytotoxic T cell epitopes from Plasmodium falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity 7, 97–112 (1997).
Aggarwal, A. et al. Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J. Exp. Med. 172, 1083–1090 (1990).
Khusmith, S. et al. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science 252, 715–718 (1991).
Doolan, D.L. et al. Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon—, and nitric oxide-dependent immunity. J. Exp. Med. 183, 1739–1746 (1996).
Ockenhouse, C.F. et al. Phase I/IIa safety, immunogenicity, and efficacy of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria. J. Infect. Dis. (in the press).
Hoffman, S.L. et al. Toward clinical trials of DNA vaccines against malaria. Immunol. Cell Biol. 75, 376–381 (1997).
Weiss, W. et al. A plasmid encoding murine GMCSF increases protection conferred by a malaria DNA vaccine. J. Immunol. (1998) (in press).
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).
Sedegah, M. et al. Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine. Proc. Natl. Acad. Sci. USA (1998) (in press).
Rodrigues, E.G., Zavala, F., Eichinger, D., Wilson, J.M. & Tsuji, M. Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria. J. Immunol. 158, 1268–1274 (1997).
Gilbert, S.C. et al. Association of malaria parasite population structure, HLA, and immunological antagonism. Science 279, 1173–1177 (1998).
Sinnis, P. & Nussenzweig, V. Preventing sporozoite invasion of hepatocytes. In: Malaria Vaccine Development: a Multi-Immune Response Approach, Hoffman, S.L. (ed.) Washington, D.C: American Society of Microbiology, pp. 15–33 (1996).
Herrington, D.A. et al. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature 328, 257–259 (1987).
Ballou, W.R. et al. Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet 1, 1277–1281 (1987).
Stoute, J.A. et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS, S Malaria Vaccine Evaluation Group. N. Engl. J. Med. 336, 86–91 (1997).
Stoute, J.A. et al. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. J. Infect. Dis. (1998) (in press).
Renia, L. et al. In vitro activity of CD4+ and CD8+ lymphocytes frommice immunized with a synthetic malaria peptide. Proc. Natl. Acad. Sci. USA 88, 7963–7967 (1991).
Wang, R. et al. Protection against malaria by Plasmodium yoelii sporozoite surface protein 1 linear peptide induction of CD4+ T cell- and IFN-γ-dependent elimination of infected hepatocytes. J. Immunol. 157, 4061–4067 (1996).
Mitchell, G.H., Butcher, G.A. & Cohen, S. Merozoite vaccination against Plasmodium knowlesi malaria. Immunology 29, 397–407 (1975).
Smythe, J.A. et al. Identification of two integral membrane proteins of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 85, 5195–5199 (1988).
Holder, A.A. & Freeman, R.R. Immunization against blood stage rodent malaria using purified parasite antigens. Nature 294, 361–366 (1982).
Hirunpetcharat, C. et al. Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein (MSP119) of Plasmodium yoelii expressed in Saccharomyces cerevisiae: correlation of protection with antigen-specific antibody titer, but not with effector CD4+ T cells. J. Immunol. 159, 3400–3411 (1997).
Bouharoun-Taylor, H., Oeuvray, C., Lunel, F. & Druilhe, P. Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J. Exp. Med. 182, 409–418 (1995).
Holder, A.A. Preventing merozoite invasion of erythrocytes. In: Malaria Vaccine Development: A Multi-Immune Response Approach, Hoffman, S.L. (ed.) Washington, D.C: American Society of Microbiology, pp. 77–104 (1996).
Patarroyo, M.E. et al. Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature 328, 629–632 (1987).
Alonso, P.L. et al. Randomised trial of efficacy of SPf6 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet 344, 1175–1181 (1994).
d'Allessandro, U. et al. Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet 346, 462–467 (1995).
Chitnis, C.E. & Miller, L.H. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J. Exp. Med. 180, 497–506 (1994).
Sim, B.K.L., Chitnis, C.E., Wasniowska, K., Hadley, T.J. & Miller, L.H. Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science 264, 1941–1944 (1994).
Su, X.-Z. et al. The large diverse gene family var encodes proteins involved in the cytoadherence and antigenic variation of Plasmodium fotoparum-infected erythrocytes. Cell 82, 89–100 (1995).
Baruch, D.I. et al. Identification of a region of PfEMPI that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood 90, 3766–3775 (1997).
Anders, R.F. Multiple cross-reactivities amongst antigens of Plasmodium falciparum impair the development of protective immunity against malaria. Parasite Immunol. 8, 529–539 (1986).
Wooton, J.C. Non-globular domains in protein sequence: automated segmentation using complexity measures. Computers Chem. 18, 269–285 (1994).
Deans, J.A., et al. Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen. Parasite Immunol. 10, 535–552 (1988).
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Miller, L., Hoffman, S. Research toward vaccines against malaria. Nat Med 4 (Suppl 5), 520–524 (1998). https://doi.org/10.1038/nm0598supp-520
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DOI: https://doi.org/10.1038/nm0598supp-520
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