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  • 1
    Publication Date: 1988-10-28
    Description: Current vaccine development strategies for malaria depend on widespread immunological responsiveness to candidate antigens such as the zygote surface antigens and the sporozoite coat protein, the circumsporozoite (CS) protein. Since immunological responsiveness is controlled mainly by genes mapping within the major histocompatibility complex (MHC), the humoral immune response to the zygote surface antigens and the cytotoxic T lymphocyte (CTL) response to the CS protein were examined in MHC-disparate congenic mouse strains. Only two of six strains responded to the 230-kilodalton zygote surface antigen and another two strains responded to the 48/45-kilodalton surface antigen. From two mouse strains, expressing between them five different class I MHC molecules, there was recognition of only a single CTL epitope from the CS protein, which was from a polymorphic segment of the molecule. The restricted CTL response to this protein parallels the restricted antibody response to this protein observed in humans and mice. These findings suggest that subunit malaria vaccines now being developed may be ineffective.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Good, M F -- Miller, L H -- Kumar, S -- Quakyi, I A -- Keister, D -- Adams, J H -- Moss, B -- Berzofsky, J A -- Carter, R -- New York, N.Y. -- Science. 1988 Oct 28;242(4878):574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2902690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Protozoan/biosynthesis ; Antigens, Protozoan/*immunology ; Antigens, Surface/genetics/immunology ; CD4-Positive T-Lymphocytes/immunology ; Genes, MHC Class II ; Immunity, Cellular ; Lymphocyte Cooperation ; Malaria/*prevention & control ; Mice ; Plasmodium falciparum/*immunology ; *Protozoan Proteins ; T-Lymphocytes, Cytotoxic/immunology ; Transfection ; Vaccines/*immunology ; Zygote/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1987-02-27
    Description: The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Good, M F -- Maloy, W L -- Lunde, M N -- Margalit, H -- Cornette, J L -- Smith, G L -- Moss, B -- Miller, L H -- Berzofsky, J A -- New York, N.Y. -- Science. 1987 Feb 27;235(4792):1059-62.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2434994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibody Formation ; Antigens, Protozoan/immunology ; Antigens, Surface/*immunology ; B-Lymphocytes/immunology ; Epitopes/*immunology ; Mice ; Peptide Fragments/chemical synthesis/*immunology ; Plasmodium falciparum/*immunology ; *Protozoan Proteins ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Helper-Inducer/*immunology ; Vaccines/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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