Skip to main content

The Use of Recombinant Proteins and Synthetic Peptides in the Development of a Plasmodium Falciparum Malaria Vaccine

  • Chapter
Book cover Modern Vaccinology
  • 107 Accesses

Abstract

It is estimated that malaria infects 300 million people of whom 120 million require clinical care and causes 1.1 million deaths each year; around 90% of these people live in Africa (TDR News, 1992). In the last ten years there has been a large increase in efforts to develop malaria vaccines, especially against the most lethal type caused by Plasmodium falciparum. Early results in humans illustrated the efficacy of irradiated sporozoites as vaccines (Clyde, 1975). The use of sporozoites, the parasite stage transferred from the mosquito vector to the animal host, as a vaccine is impractical but their efficacy demonstrates that, while the ability of the parasite to complete its life cycle is destroyed by irradiation, protective antigens are not. The search for the protective antigen(s) led to the identification of the major surface protein of the sporozoite, the circumsporozoite protein (CSP) and its main repeat epitope, Asn-Ala-Asn-Pro (NANP), as a prime vaccine candidate (Zavala et al., 1985). A pathogen’s structures that are recognized by protective antibodies, e.g. (NANP)3, or T lymphocytes can be termed “protectopes.” (NANP)n, in the form of a synthetic peptide (Herrington et al., 1987) or a recombinant protein (Ballou et al., 1987), was the primary parasite sequence used in the initial clinical vaccine studies. The limited success of these vaccine trials has led to additional efforts to improve vaccine efficacy including further analyses of protective mechanisms and antigens in animal models, evaluation of the association between HLA and disease prevalence in human beings living in malaria endemic areas and the specificity of antibody and T cells from people in malaria vaccine trial or endemic areas to P. falciparum-derived antigens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aggarwal, A., Kumar, S., Jaffe, R., Hone, D., Gross, M. and Sadoff, J. (1990). Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J. Exp. Med. 172: 1083–1090.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, P., Pichichero, M.E. and Insel, R.A. (1985). Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae Type b coupled to diphtheria toxoid or the toxin protein CRM 197. J. Clin. Invest. 76: 52–59.

    Article  PubMed  CAS  Google Scholar 

  • Amador, R., Moreno, A., Valero, V., Murillo, L., Mora, A.L., Rojas, M., Rocha, C., Salcedo, M., Guzman, F., Espejo, F., Nunez, F. and Patarroyo, M.E. (1992). The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity. Vaccine. 10: 179–184.

    Article  PubMed  CAS  Google Scholar 

  • Ballou, W.R., Sherwood, J.A., Neva, F.A., Gordon, D.M., Wirtz, R.A., Wasserman, G.F., Diggs, C.L., Hoffman, S.L., Hollingdale, M.R., Hockmeyer, W.T., Schneider, I., Young, J.F., Reeve, P. and Chulay, J.D. (1987). Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. The Lancet i:. 1277–1281.

    Article  Google Scholar 

  • Blackman, M.J., Heidrich, H.-G., Donachie, S., McBride, J.S. and Holder, A.A. (1990). A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J. Exp. Med. 172: 379–382.

    Article  PubMed  CAS  Google Scholar 

  • Brake, D.A., Long, C.A. and Weidanz, W.P. (1988). Adoptive protection against Plasmodium chaboudi adami malaria in athymic nude mice by a cloned T cell line. J. Immunol. 140: 1989–1993.

    PubMed  CAS  Google Scholar 

  • Briles, D.E., Forman, C., Hudak, S. and Claflin, J.L. (1984). The effects of idiotype on the ability of IgGl anti-phosphorylcholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae. Eur. J. Immuunol. 14: 1027–1030.

    Article  CAS  Google Scholar 

  • Burns, J.M., Majarian, W.R., Young, J.F., Daly, T.M. and Long, C.A. (1989). A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoelii. J. immunol. 143: 2670–2676.

    PubMed  CAS  Google Scholar 

  • Cerami, C., Frevert, U., Sinnis, P., Takacs, B., Clavijo, P., Santos, M.J. and Nussenzweig, V. (1992). The basolateral domain of the hepatoma plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites. Cell. 70: 1021–1033.

    Article  PubMed  CAS  Google Scholar 

  • Chang, S.P., Gibson, H.L., Lee-ng, C.T., Barr, P.J. and Hui, G.S.M. (1992). A carboxyl-terminal fragment of Plasmodium falciparum gp195 expressed by a recombinant baculovirus induces antibodies that completely inhibit parasite growth. J. Immunol. 149: 548–555.

    PubMed  CAS  Google Scholar 

  • Charoenvit, Y., Mellouk, S., Cole, C., Bechara, R., Leef, M.F., Sedegah, M., Yuan, L.F., Robey, F.A., Beaudoin, R.L. and Hoffman, S.L. (1991a). Monoclonal but not polyclonal, antibodies protect against Plasmodium yoelii sporozoites. J. Immunol. 146: 1020–1025.

    PubMed  CAS  Google Scholar 

  • Charoenvit, Y., Collins, W.E., Jones, T.R., Millet, P., Yuan, L., Campbell, G.H., Beaudoin, R.L., Broderson, J.R. and Hoffman, S.L. (1991b). Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence. Science. 251: 668–671.

    Article  PubMed  CAS  Google Scholar 

  • Chulay, J.D. (1989). Development of sporozoite vaccines for malaria. Trans. Roy. Soc. Trop. Med. Hyg. 83: Suppl. 61–66.

    Article  Google Scholar 

  • Clyde, D.F. (1975). Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am. J. Trop. Med. 24: 397–401.

    CAS  Google Scholar 

  • Collins, W.E., Anders, R.F., Pappaioanou, M., Campbell, G.H., Brown, G.V., Kemp, D.J., Coppel, R.L., Skinner, J.C., Andrysiak, P.M., Favaloro, J.M., Corcoran, L.M., Broderson, J.R., Mitchell, G.F. and Campbell, C.C. (1986). Immunization of aotus monkeys with recombinant proteins of an erythrocyte surface antigen of Plasmodium falciparum. Nature 323: 259–262.

    Article  PubMed  CAS  Google Scholar 

  • Cooper, J.A., Cooper, L.T. and Saul, A.J. (1992). Mapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA1. Mol. Biochem. Parasit. 51: 301–312.

    Article  CAS  Google Scholar 

  • Deres, K., Schild, H., Wiesmuller, K.-H., Jung, G. and Rammensee, H.-G. (1989). In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature. 342: 561–564.

    Article  PubMed  CAS  Google Scholar 

  • Di. John, D., Torres, J.R., Murillo, J., Herrington, D.A., Wasserman, S.S., Cortesia, M.J., Losonsky, G.A., Sturchler, D. and Levine, M.M. (1989). Effect of priming with carrier on response to conjugate vaccine. Lancet. ii: 1415–1418.

    Article  Google Scholar 

  • Etlinger, H.M., Heimer, E.P., Trzeciak, A., Felix, A.M. and Gillessen, D. (1988a). Assessment in mice of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, P. falciparum. Immunol. 64: 551–558.

    CAS  Google Scholar 

  • Etlinger, H.M., Felix, A.M., Gillessen, D., Heimer, E.P., Just, M., Pink, J.R.L., Sinigaglia, F., Sturchler, D., Takacs, B., Trzeciak, A. and Matile, H. (1988b). Assessment in humans of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, P. falciparum. J. Immunol. 140: 626–633.

    PubMed  CAS  Google Scholar 

  • Etlinger, H.M., Gillessen, D., Lahm, H.-W., Matile, H., Schonfeld and Trzeciak, A. (1990). Use of prior vaccinations for the development of new vaccines. Science. 249: 423–425.

    Article  PubMed  CAS  Google Scholar 

  • Etlinger, H.M. and Knorr, R. (1991a). Model using a peptide with carrier function for vaccination against different pathogens. Vaccine. 9: 512–514.

    Article  PubMed  CAS  Google Scholar 

  • Etlinger, H.M., Caspers, P., Matile, H., Schonfeld, H.-J., Stuber, D. and Takacs, B. (1991b). Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. Infect. Immun. 59: 3498–3503.

    PubMed  CAS  Google Scholar 

  • Etlinger, H.M. (1992). Carrier sequence selection-one key to successful vaccines. Immunol. Today. 13: 52–55.

    Article  PubMed  CAS  Google Scholar 

  • Fries, L.F., Gordon, D.M., Schneider, I., Beier, J.C., Long, G.W., Gross, M., Que, J.U., Cryz, S.J. and Sadoff, J.C. (1992a). Safety, immunogenicity, and efficacy of a Plasmodium falciparum vaccine comprising a circumsporozoite protein repeat region peptide conjugated to Pseudomonas aeruginosa toxin A. Infect. Immun. 60: 1834–1839.

    PubMed  CAS  Google Scholar 

  • Fries, L.F., Gordon, D.M., Richards, R.L., Egan, J.E., Hollingdale, M.R., Gross, M., Silverman, C. and Alving, C.R. (1992). Liposomal malaria vaccine in humans: A safe and potent adjuvant strategy. Proc. Natl. Acad. Sci. 89: 358–362.

    Article  PubMed  CAS  Google Scholar 

  • Galelli, A. and Chariot, B. (1990). Clonal anergy of memory B cells in epitope-specific regulation. J. Immunol. 145: 2397–2405.

    PubMed  CAS  Google Scholar 

  • Guar, A., Aruna, K., Singh, O. and Talwar, G.P. (1990). Bypass by an alternate “carrier” of acquired unresponsiveness to hCG upon repeated immunization with tetanus-conjugated vaccine. Int. Immunol. 2: 151–155.

    Article  Google Scholar 

  • Guiguemde, T.R., Sturchler, D., Ouedraogo, J.B., Drabo, M., Etlinger, H.M., Douchet, C., Gbary, A.R., Haller, L., Kambou, S., and Fernex, M. (1990). Vaccxination contre le Paludisme: premier en Afrique (Bobo-Dioulasso, Burkina Faso). Bull. Soc. Path. Ex. 83: 217–227.

    CAS  Google Scholar 

  • Herrera, S.M., Herrera, A., Perlaza, L., Burki, Y., Caspers, P., Boebeli, H., Rotmann, D. and Certa, U. (1990). Immunization of Aotus monkeys with Plasmodium falciparum blood stage recombinant proteins. Proc. Natl Acad. Sci. 87: 4017–4021.

    Article  PubMed  CAS  Google Scholar 

  • Herrington, D.A., Clyde, D.F., Losonsky, G., Cortesia, M., Davis, J., Murphy, J.R. Felix, A.M., Heimer, E.P., Gillessen, D., Nardin, E., and Nussenzweig, R.S.N. (1987). Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature (Lond.). 328: 257–259.

    Article  CAS  Google Scholar 

  • Herrington, D.A., Losonsky, G.A., Smith, G., Volvovitz, F., Cochran, J., Jackson, K., Hoffmann, S.L., Gordon, D.M., Leine, M.M. and Edelman, R. (1992). Sarety and immunogenicity in volunteers of a recombinant Plasmodium falciparum circunsporozoite protein malaria vaccine produced in Lepidopteran cells. Vaccine. 10: 841–846.

    Article  PubMed  CAS  Google Scholar 

  • Herzenberg, L.A. and Tokuhisa, T. (1982). Epitope-specific regulation 1. Carrier-specific induction of suppression for IgG anti-hapten antibody responses. J. Exp. Med. 155: 1730–1740.

    Article  PubMed  CAS  Google Scholar 

  • Hill, A.V.S., Elvin, J., Willis, A.C., Aidoo, M., Allsopp, C.E.M., Gotch, F.M., Gao, M., Takiguchi, M., Greenwood, B.M., Townsend, A.R.M., McMicahel, A.J. and Whittle, H.C. (1992). Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 360: 434–439.

    Article  PubMed  CAS  Google Scholar 

  • Hoffman, S.L., Oster, C.N., Mason, C., Beier, J.C, Sherwood, J.A., Ballou, W.R., Mugambi, M. and Chulay, J.D. (1989). Human lymphocyte proliferative response to sporozoite T cell epitope correlates with resistance to falciparum malaria. J. Immunol. 142: 1299–1303.

    PubMed  CAS  Google Scholar 

  • Hui, G.S., Chang, S.P., Gibson, H., Hashimoto, A., Hashiro, C., Barr, P.J. and Kotani, S. (1991). Influence of adjuvants on the antibody specificity to the Plasmodium falciparum major merozoite surface protein. gp195. J. Immunol. 147: 3935–3941.

    PubMed  CAS  Google Scholar 

  • Inselburg, J., Bzik, D.J., Li, W.-B., Green, K.M., Kansopon, J., Hahm, B.K., Bathurst, I.C., Barr, P.J. and Rossan, R.N. (1991). Protective immunity induced in aotus monkeys by recombinant SERA proteins of Plasmodium falciparum. Infect. Immun. 59: 1247–1250.

    PubMed  CAS  Google Scholar 

  • Just, M., Berger, R., Sturchler, D., Etlinger, H.M., Fernex, M., Gillessen, D., Matile, H., Pink, J.R.L., Sinigalglia, F., and Takacs, B. (1989). Antibody response to malaria sporozoite vaccine enhanced by simultaneous administration of alpha-travel medicine. R. Steffen, H.O., Lobel, J. Haworth and D.J. Bradley, eds., Berlin, Springer-Verlang, pp. 262–264.

    Google Scholar 

  • Kaslow, D.C., Isaacs, S.M., Quakyi, I.A., Gwadz, R.W., Moss, B. and Keister, D.B. (1991). Induction of Plasmodium falciparum transmission-blocking antibodies by recombinant vaccinia virus. Science. 252: 1310–1313.

    Article  PubMed  CAS  Google Scholar 

  • Khusmith, S., Charoenvit, Y., Kumar, S., Sedegah, M., Beaudoin, R.L. and Hoffman, S.L. (1991). Science. 252: 715–718.

    Article  PubMed  CAS  Google Scholar 

  • Knapp, B. Shaw, A., Hundt, E., Enders, B. and Kupper, H.A. (1988). A histidine alanine rich recombinant antigen protects aotus monkeys from P. falciparum infection. Behring lnst. Mitt. 82: 349–359.

    CAS  Google Scholar 

  • Kumar, S., Miller, L.H., Quakyi, I.A., Keister, D.B., Houghten, R.A., Maloy, W.L., Moss, B., Berzofsky, J.A. and Good, M.F. (1988). Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature. 334: 258–260.

    Article  PubMed  CAS  Google Scholar 

  • Majarian, W.R., Daly, T.M., Weidanz, W.P. and Long, C.A. (1984). Passive immunization against murine malaria with an IgG3 monoclonal antibody. J. Immunol. 132: 3131–3137.

    PubMed  CAS  Google Scholar 

  • Malik, A., Egan, J.E., Houghten, R.A. and Hoffman, S.L. (1991). Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc. Natl. Acad. Sci. 88: 3300–3304.

    Article  PubMed  CAS  Google Scholar 

  • Molano, A., Segura, C., Guzman, F., Lozada, D. and Patarroyo, M.E. (1992). In human malaria protective antibodies are directed mainly against the Lys-Glu ion pair within the Lys-Glu-Lys motif of the synthetic vaccine SPf66. Par. Immunol. 14: 111–124.

    Article  CAS  Google Scholar 

  • Patarroyo, M.E., Amador, R., Clavijo, P., Moreno, A., Guzman, F., Romero, P., Tascon, R., Franco, A., Murillo, L.A., Ponton, G., and Trujillo, G. (1988). A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature 332: 158–161.

    Article  PubMed  CAS  Google Scholar 

  • Potocnjak, P., Yoshida, M., Nussenzweig, R.S. and Nussenzweig, V. (1980). Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J. Exp. Med. 129: 1504–1513.

    Article  Google Scholar 

  • Rickman, L.S., Gordon, D.M., Wistar, Jr. R., Krzych, U., Gross, M., Hollingdale, M.R., Egan, J.E., Chulay, J.D. and Hoffmann, S.L. (1991). Use of adjuvant containing mycobacterial cell-wall skeleton, monophosphoryl lipid A, and squaline in malaria circumsporozoite protein vaccine. Lancet. 337: 998–1001.

    Article  PubMed  CAS  Google Scholar 

  • Rawlings, D.J. and Kaslow, D.C. (1992). Adjuvant-dependent immune response to malarial transmission-blocking vaccine candidate antigens. J. Exp. Med. 176: 1483–1487.

    Article  PubMed  CAS  Google Scholar 

  • Ridley, R.G., Takacs, B., Etlinger, H.M., and Scaife, J.G. (1990). A rhoptry antigen of Plasmodium falciparum is protective in Saimiri monkeys. Parasitology. 101: 187–192.

    Article  PubMed  Google Scholar 

  • Rodgers, W.O., Malik, A., Mellouk, S., Nakamura, K., Rogers, M.D., Szarfman, A., Gordon, D.M., Nussler, A.K., Aikawa, M. and Hoffman, S.L. (1992). Characterization of Plasmodium falciparum sporozoite surface protein 2. Proc. Natl. Acad. Sci. 89: 9176–9180.

    Article  Google Scholar 

  • Romero, P., Maryanski, J.L., Corradin, G., Nussenzweig, R.S., Nussenzweig, V. and Zavala, F. (1989). Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 341: 323–325.

    Article  PubMed  CAS  Google Scholar 

  • Sacci, J.B., Schriefer, M.E., Resau, J.H. Wirtz, R.A., Detolla, Jr., L.J., Markham, R.B. and Azad, A.F. (1992). Mouse model for exoerythrocytic stages of Plasmodium falciparum malaria parasite. Proc. Natl. Acad. Sci. 89: 358–362.

    Article  Google Scholar 

  • Sad, S., Rao, K., Arora, R., Talear, G.P. and Raghupathy, R. (1992). Bypass of carrier-induced epitope-specific suppression using a T-helper epitope. Immunol. 76: 599–603.

    CAS  Google Scholar 

  • Schofield, L., Villaquiran, J., Ferreira, A., Schellekens, H., Nussenzweig, R. and Nussenzweig, V. (1987). γ interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 330: 664–666.

    Article  PubMed  CAS  Google Scholar 

  • Schutze, M.-P., Leclerc, C., Vogel, F.R. and Chedid, L. (1987). Epitopic suppression in synthetic vaccine models: analysis of the effector mechanisms. Cell. Immunol. 104: 79–90.

    Article  PubMed  CAS  Google Scholar 

  • Sedegah, M., Kim Lee Sim, B., Mason, C., Nutman, T., Malik, A., Roberts, C., Johnson, A., Ochola, J., Koech, D., Were, B. and Hoffman, S.L. (1992). Naturally acquired CD8+ cytotoxic T 1 lymphocytes against the Plasmodium falciparum circumsporozoite protein. J. Immunol. 149: 966–971.

    PubMed  CAS  Google Scholar 

  • Sercarz, E. and Krzych, U. (1991). The distinctive specificity of antigen-specific suppressor T cells. Immunol. Today. 8: 111–118.

    Article  Google Scholar 

  • Siddiqui, W.A., Tarn, L.Q., Kan, S.-C., Kramer, K.J., Case, S.E., Palmer, K.L., Yamaga, K.M. and Hui, G.S.N. (1986). Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in aotus monkeys. Infect. Immun. 52: 314–318.

    PubMed  CAS  Google Scholar 

  • Smythe, J.A., Coppel, R.L., Brown, G.V., Ramasamy, R., Kemp, D.J. and Anders, R.F. (1988). Identification of two integral membrane proteins of Plasmodium falciparum. Proc. Natl. Acad. Sci. 85: 5195–5199.

    Article  PubMed  CAS  Google Scholar 

  • Sturchler, D., Berger, R., Etlinger, H.M., Fernex, M., Matile, H., Pink, J.R.L., Schlumbom, V., and Just, M. (1989). Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults. Vaccine. 7: 457–461.

    Article  PubMed  CAS  Google Scholar 

  • Sturchler, D., Zimmer, G., Berger, R., Etlinger, H.M., Fernex, M., Matile, H., and Just, M. (1990). Interfon-alpha and synthetic peptide malaria sporozoite vaccine in non-immune adults: antibody response after 40 weeks. Bull. WHO, 68 (Suppl.): 38–41.

    PubMed  Google Scholar 

  • Sturchler, D. Just, M., Berger, R., Reber-Liske, R., Matile, H., Etlinger, H., Takacs, B., Rudin, C. and Fernex, M. (1991). Evaluation of 5.1-(NANP)19, a recombinant Plasmodium falciparum vaccine candidate, in adults. Tropical Geographical Med. 44: 9–14.

    Google Scholar 

  • Tagawa, M., Tokuhisa, T., Ono, K., Taniguchi, M., Herzenberg, L.A. and Herzenberg, L.A. (1984). Epitopic-specific regulation IV. In vitro studies with suppressor T cells induced by carrier/hapten-carrier immunization. Cell. Immunol 86: 327–336.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, H., Takeshita, T., Morein, B., Putney, S., Germain, R.N. and Berzofsky, J.A. (1990). Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature. 344: 873–875.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, M, Romero, P., Nussenzweig, R.S. and Zavala, F. (1990). CD4+ cytolytic T cell clone confers protection against murine malaria. J. Exp. Med. 172: 1353–1357.

    Article  PubMed  CAS  Google Scholar 

  • TDR news (1992). Personal perspective, UNDP/World Bank/ WHO No. 41. p. 3.

    Google Scholar 

  • Vermeulen, A.N., Ponnudurai, T., Beckers, P.J.A., Verhave, J.-P., Smits, M.A. and Meuwissen, J. H.E. Th. (1985). Sequential expressin of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J. Exp. Med. 162: 1460–1476.

    Article  PubMed  CAS  Google Scholar 

  • Vreden, S.G.S., Verhave, J.P., Oettinger, T., Sauerwein, R.W. and Meuwissen, J.H.E.T. (1991). Phase I clinical trial of a recombinant malaria vaccine consisting of the circumsporozoite repeat region of Plasmodium falciparum coupled to hepatitis B surface antigen. Am J. Trop. Med. Hyg. 45: 533–538.

    PubMed  CAS  Google Scholar 

  • Wiess, W.S., Mellouk, S., Houghten, R.A., Sedegah, M., Kumar, S., Good, M.S., Berzofsky, J.A., Miller, L.H. and Hoffman, S.L. (1990). Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J. Exp. Med. 171: 763–773.

    Article  Google Scholar 

  • Zavala, F., Tarn, J.P., Cochrane, A.H., Quakyi, I., Nussenzweig, R.S., and Nussenzweig, (1985). Rationale for development of a synthetic vaccine against Plasmodium falciparum malaria. Science. 228: 1436–1440.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Etlinger, H.M. (1994). The Use of Recombinant Proteins and Synthetic Peptides in the Development of a Plasmodium Falciparum Malaria Vaccine. In: Kurstak, E. (eds) Modern Vaccinology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1450-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-1450-7_18

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1452-1

  • Online ISBN: 978-1-4899-1450-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics