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The Journal of Immunology, Vol 157, Issue 9 4061-4067, Copyright © 1996 by American Association of Immunologists

ARTICLES

Protection against malaria by Plasmodium yoelii sporozoite surface protein 2 linear peptide induction of CD4+ T cell- and IFN-gamma- dependent elimination of infected hepatocytes

R Wang, Y Charoenvit, G Corradin, P De La Vega, ED Franke and SL Hoffman
The Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889, USA.

Plasmodium falciparum sporozoite surface protein 2 (SSP2), also known as TRAP, is included in experimental human malaria vaccines because Plasmodium yoelii SSP2 is the target of protective CD8+ CTL that eliminate P. yoelii-infected hepatocytes in mice. We now report that immunization with a synthetic branched-chain peptide including four copies of a PySSP2 sequence, NPNEPS, and two tetanus toxin T helper epitopes in the adjuvant TiterMax, or with an 18 amino acid peptide (NPNEPS)3 in the adjuvant protects A/J, but not BALB/c or C57BL/6 mice. Transfer of T lymphocyte-enriched immune splenocytes protects naive mice; in vivo depletion of CD4+ T cells eliminates vaccine-induced protection; and in vivo treatment with anti-IFN-gamma reverses vaccine- induced activity against infected hepatocytes. Lymph node cells from immunized A/J, BALB/c, and C57BL/6 mice recognize the (NPNEPS)3 peptide in vitro. However, the protected A/J mice respond with a predominantly Th1 pattern of lymphocyte response, and the non-protected strains of mice respond with a Th2 pattern. There are many examples of CD4+ T cells transferring protection against infectious organisms. However, to our knowledge, this is the first formal demonstration that immunization with a linear synthetic peptide induces CD4+ T cell-dependent, IFN- gamma dependent, genetically restricted sterile protective immunity against an infectious agent.


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