Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein

Authors

  • Dona Yamuna Munesinghe,

    1. Department of Zoology, New York University, New York
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    • Recipient of a Fulbright-Hays Fellowship.

  • Pedro Clavijo,

    1. University of Colombo, Sri Lanka and Department of Medical and Molecular Parasitology, New York University, New York
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  • Mauricio Calvo Calle,

    1. University of Colombo, Sri Lanka and Department of Medical and Molecular Parasitology, New York University, New York
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  • Ruth S. Nussenzweig,

    1. University of Colombo, Sri Lanka and Department of Medical and Molecular Parasitology, New York University, New York
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  • Elizabeth Nardin

    Corresponding author
    1. University of Colombo, Sri Lanka and Department of Medical and Molecular Parasitology, New York University, New York
    • Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA
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Abstract

The immunogenicity of multiple antigen peptides (MAP) constructs containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite (CS) protein was examined in vitro, using a human T cell clone, and in vivo, using four different strains of mice. All the MAP constructs that contained the T cell epitope, (DPNANPNVDPNANPNV), stimulated proliferation and interferon-γ production by a human T cell clone specific for this epitope which is located in the 5′ end of the repeat region of the P. falciparum CS protein. These human T cells did not recognize MAP that contained only the B cell epitope, (NANP)3, which is located in the 3′ repeat region. Optimal antibody responses were obtained in mice immunized with MAP containing four copies of tandemly arranged T and B cell epitopes, (TB)4. The murine immune response to the MAP constructs was genetically restricted. Mice of a high responder strain, C57BL, recognized both the 5′ and 3′ repeat sequences in the MAP as T, as well as B, cell epitopes and developed very high anti-MAP and anti-sporozoite antibody titers. A/J and C3H mice, which were intermediate responders, developed lower antibody titers which varied according to the orientation of the T vs. the B cell epitopes within the MAP constructs. BALB/c mice were nonresponders and did not develop antibodies following immunization with any of the MAP constructs containing the 5′ and 3′ repeats of the P. falciparum CS protein.

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