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The 19-kDa C-terminal region of merozoite surface protein 1 (MSP1(19)), a major blood stage malaria vaccine candidate, is the target of cellular and humoral immune responses in humans naturally infected with Plasmodium falciparum. We have previously described engineered variants of this protein, designed to be better vaccine candidates, but the human immune response to these proteins has not been characterized fully. Here we have investigated the antigenicity of one such variant compared to wild-type MSP1(19)-derived protein and peptides. Gambian adults produced both high T helper type 1 (Th1) [interferon (IFN)-γ] and Th0/Th2 [interleukin (IL)-13 and sCD30] responses to the wild-type MSP1(19) and the modified protein as wells as to peptides derived from both forms. Response to the modified MSP1(19) (with three amino acid substitutions: Glu27Tyr, Leu31Arg and Glu43Leu) relative to the wild-type, included higher IFN-γ production. Interestingly, some peptides evoked different patterns of cytokine responses. Modified peptides induced higher IL-13 production than the wild-type, while the conserved peptides P16 and P19 induced the highest IFN-γ and IL-13 and/or sCD30 release, respectively. We identified P16 as the immunodominant peptide that was recognized by cells from 63% of the study population, and not restricted to any particular human leucocyte antigen D-related (HLA-DR) type. These findings provide new and very useful information for future vaccine development and formulation as well as potential Th1/Th2 immunmodulation using either wild-type or modified protein in combination with their peptides.

Original publication

DOI

10.1111/j.1365-2249.2011.04467.x

Type

Journal article

Journal

Clin Exp Immunol

Publication Date

12/2011

Volume

166

Pages

366 - 373

Keywords

Antigens, Protozoan, CD4-Positive T-Lymphocytes, Cytokines, Gambia, HLA-DR Antigens, Humans, Interferon-gamma, Interleukin-13, Ki-1 Antigen, Malaria Vaccines, Malaria, Falciparum, Merozoite Surface Protein 1, Plasmodium falciparum, Protozoan Proteins, Recombinant Proteins, Th1 Cells, Th1-Th2 Balance, Th2 Cells, Vaccines, Synthetic