The Journal of Immunology, Vol 154, Issue 6 2784-2793, Copyright © 1995 by American Association of Immunologists

ARTICLES

Induction of protective polyclonal antibodies by immunization with a Plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine [published erratum appears in J Immunol 1995 Aug 1;155(3):1637]

R Wang, Y Charoenvit, G Corradin, R Porrozzi, RL Hunter, G Glenn, CR Alving, P Church and SL Hoffman
Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889.

Monoclonal Abs against the repeat region of the circumsporozoite protein (CSP) completely protect mice against Plasmodium yoelii (Py), but synthetic peptide and recombinant protein vaccines designed to produce only Abs to the PyCSP repeat region have never been reported to consistently provide protection. This lack of protection in the rodent model system has predicted the poor protection achieved in humans after immunization with synthetic peptide and recombinant protein P. falciparum CSP vaccines and has raised serious questions regarding the capacity for vaccine-induced polyclonal Abs against the CSP to consistently protect humans. We now report immunization studies with a multiple Ag peptide vaccine designed to rely on "universal" T epitopes from tetanus toxin to produce T cell help for induction of protective Abs against the repeat region of the PyCSP. When delivered with a nonionic block co-polymer adjuvant, the vaccine protected 78 to 100% of three inbred strains of mice, and 100% of outbred mice against P. yoelii sporozoite challenge. Protection was associated with Ab titer, and passive transfer of purified IgG from immune mice protected naive recipients. Similar protection was achieved when the peptide was encapsulated in liposomes with lipid A and mixed with aluminum hydroxide. By demonstrating for the first time solid protection against P. yoelii by polyclonal Abs against the CSP, these data provide the rationale for assessment of a similarly constructed and formulated P. falciparum CSP multiple Ag peptide vaccine in humans.

This article has been cited by other articles:

				E. H. Nardin, J. M. Calvo-Calle, G. A. Oliveira, R. S. Nussenzweig, M. Schneider, J.-M. Tiercy, L. Loutan, D. Hochstrasser, and K. Rose A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types J. Immunol., January 1, 2001; 166(1): 481 - 489. [Abstract] [Full Text] [PDF]

				M. Sedegah, W. Weiss, J. B. Sacci Jr., Y. Charoenvit, R. Hedstrom, K. Gowda, V. F. Majam, J. Tine, S. Kumar, P. Hobart, et al. Improving Protective Immunity Induced by DNA-Based Immunization: Priming with Antigen and GM-CSF-Encoding Plasmid DNA and Boosting with Antigen-Expressing Recombinant Poxvirus J. Immunol., June 1, 2000; 164(11): 5905 - 5912. [Abstract] [Full Text] [PDF]

				Y. Charoenvit, V. F. Majam, G. Corradin, J. B. Sacci Jr., R. Wang, D. L. Doolan, T. R. Jones, E. Abot, M. E. Patarroyo, F. Guzman, et al. CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii 17-Kilodalton Hepatocyte Erythrocyte Protein Infect. Immun., November 1, 1999; 67(11): 5604 - 5614. [Abstract] [Full Text] [PDF]

				J. A. Vaughan, L. F. Scheller, R. A. Wirtz, and A. F. Azad Infectivity of Plasmodium berghei Sporozoites Delivered by Intravenous Inoculation versus Mosquito Bite: Implications for Sporozoite Vaccine Trials Infect. Immun., August 1, 1999; 67(8): 4285 - 4289. [Abstract] [Full Text] [PDF]

				A. Bharadwaj, P. Sharma, S. K. Joshi, B. Singh, and V. S. Chauhan Induction of Protective Immune Responses by Immunization with Linear Multiepitope Peptides Based on Conserved Sequences from Plasmodium falciparum Antigens Infect. Immun., July 1, 1998; 66(7): 3232 - 3241. [Abstract] [Full Text] [PDF]