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  • 1
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    Online Resource
    Cellular and humoral immune responses to well-defined blood stage antigens (major merozoite surface antigen) of Plasmodium falciparum in adults from an Indian zone where malaria is endemic
    American Society for Microbiology ; 1994
    In:  Infection and Immunity Vol. 62, No. 2 ( 1994-02), p. 685-691
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 62, No. 2 ( 1994-02), p. 685-691
    Abstract: Conserved and variant regions of two blood stage vaccine candidate antigens of Plasmodium falciparum, merozoite surface antigen (MSA-1) and ring-infected erythrocyte surface antigen (Pf155/RESA), have been shown to be immunogenic. However, the relative immunogenicity of these immunogens in different populations has not been studied. The conserved N-terminal region of MSA-1 was investigated for its immunogenicity by studying cellular (T cell) and humoral (B cell) immune responses in P. falciparum-primed individuals, living in malaria-hyperendemic areas (Orissa State, India), where malaria presents an alarming situation. MSA-1-derived synthetic peptides contained sequences that activated T cells to proliferate and release gamma interferon in vitro. There was considerable variation in the responses to different peptides. However, the highest responses (51% [18 of 35] by proliferation and 34% [12 of 35] by gamma interferon release) were obtained with a synthetic hybrid peptide containing sequences from conserved N- and C-terminal repeat regions of MSA-1 and Pf155/RESA, respectively. Antibody reactivities in an enzyme immunoassay of plasma samples from these donors to different peptides used for T-cell activation were heterogeneous. In general, there was poor correlation between DNA synthesis and either gamma interferon release or antibody responses in individual donors, underlining the importance of examining several parameters of T-cell activation to assess the total T-cell responsiveness of a study population to a given antigen. However, the results from our studies suggest that synthetic constructs containing sequences from the N- and C-terminal regions of MSA-1 and Pf155/RESA representing different erythrocytic stages of the P. falciparum parasite are more immunogenic in humans living in malaria-hyperendemic areas of India who have been primed by natural infection.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/iai.62.2.685-691.1994
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1994
    detail.hit.zdb_id: 1483247-1
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  • 2
    Online Resource
    Online Resource
    Human immune response in Plasmodium falciparum malaria. Synthetic peptides corresponding to known epitopes of the Pf155/RESA antigen induce production of parasite-specific antibodies in vitro.
    The American Association of Immunologists ; 1991
    In:  The Journal of Immunology Vol. 147, No. 7 ( 1991-10-01), p. 2295-2301
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 147, No. 7 ( 1991-10-01), p. 2295-2301
    Abstract: Autologous cell mixtures containing T cells, B cells, and adherent accessory cells from individuals primed to the malaria parasite Plasmodium falciparum by repeated natural infections were investigated for induction of Ig and antibody secretion in vitro. In vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant T cell epitopes of the merozoite Ag ring-infected erythrocyte surface Ag (Mr 155,000) (Pf155/RESA), one from its carboxyl-terminal repeat and one from its nonrepeated amino-terminal region, gave rise to significant IgG secretion. Supernatants from lymphocyte cultures activated with either one of these peptides contained antibodies reacting with P. falciparum Ag in immunofluorescence assays and with Pf155/RESA peptides in a slot blot assay. No anti-P. falciparum antibodies were induced in the medium controls by lymphocyte stimulation with either tetanus toxoid or PWM. Induction in vitro of anti-Pf155/RESA antibodies was correlated with the presence of such antibodies in the sera of the lymphocyte donors, suggesting that the induction of antibody secretion reflected a secondary response in vitro of in vivo primed cells. Inspection of antibody profiles in individual donors revealed that the peptide corresponding to a sequence in the 3' repeat region induced anti-Pf155/RESA peptide antibodies reacting with identical or related and cross-reacting sequences in the 3' or 5' repeat region of the molecule. In contrast, the peptide corresponding to a nonrepeated T cell epitope in the amino terminus of the molecule only induced antibodies to an immunodominant amino-terminal B cell epitope partly overlapping with the T cell reactive sequence. Similar findings were made in the lymphocyte donors' plasma, frequently displaying significant correlations between antibody reactivities to the repeat peptides but not between these reactivities and those to the amino-terminal peptide. The marked specificity of this antibody formation in vitro suggests an underlying process of cognate recognition involving Ag-specific T and B cells reacting with different segments of the inducer peptide. The present experimental system should be well suited for identification of Th epitopes capable of inducing the production of antibodies of defined specificity in the human system.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.147.7.2295
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1991
    detail.hit.zdb_id: 1475085-5
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  • 3
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    Online Resource
    Characterization of regulatory T cell responses to defined immunodominant T cell epitopes of the Plasmodium falciparum antigen Pf155/RESA
    Elsevier BV ; 1990
    In:  Immunology Letters Vol. 25, No. 1-3 ( 1990-8), p. 129-134
    Details
    In: Immunology Letters, Elsevier BV, Vol. 25, No. 1-3 ( 1990-8), p. 129-134
    Type of Medium: Online Resource
    ISSN: 0165-2478
    URL: Article
    DOI: 10.1016/0165-2478(90)90103-W
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1990
    detail.hit.zdb_id: 2013171-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Construction of a synthetic immunogen: use of the natural immunomodulator polytuftsin in malaria vaccines against RESA antigen of Plasmodium falciparum
    Elsevier BV ; 1994
    In:  Vaccine Vol. 12, No. 9 ( 1994), p. 819-824
    Details
    In: Vaccine, Elsevier BV, Vol. 12, No. 9 ( 1994), p. 819-824
    Type of Medium: Online Resource
    ISSN: 0264-410X
    URL: Article
    DOI: 10.1016/0264-410X(94)90291-7
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1994
    detail.hit.zdb_id: 1468474-3
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  • 5
    Online Resource
    Online Resource
    Number of cells from Plasmodium falciparum-immune donors that produce gamma interferon in vitro in response to Pf155/RESA, a malaria vaccine candidate antigen
    American Society for Microbiology ; 1990
    In:  Infection and Immunity Vol. 58, No. 9 ( 1990-09), p. 2989-2994
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 58, No. 9 ( 1990-09), p. 2989-2994
    Abstract: Secretion of gamma interferon (IFN-gamma) in response to stimulation of Plasmodium falciparum-primed T cells by specific antigens may be a useful indicator of cellular immunity to malaria. An enzyme-linked immunospot (ELISPOT) assay designed to detect IFN-gamma at the single-cell level was used to study IFN-gamma-producing cells from P. falciparum-primed donors from The Gambia after in vitro stimulation with various malarial antigens. IFN-gamma secreted into the culture supernatant was measured by conventional enzyme-linked immunosorbent assay (ELISA). There was a good correlation in individual donors between the level of IFN-gamma secreted into the culture supernatant and the number of IFN-gamma-secreting cells. However, the ELISPOT assay was apparently more sensitive in demonstrating low levels of IFN-gamma production than the ELISA was. Thus after stimulation with crude P. falciparum antigen from infected erythrocytes, 72% of the primed donors responded positively in the ELISPOT assay but only 55% responded positively in the ELISA. When stimulated with synthetic peptides representing immunodominant epitopes of the malarial antigen Pf155/RESA, a vaccine candidate, 31 to 55% responded in the ELISPOT assay and 21 to 36% responded in the ELISA. Unprimed Europeans did not respond positively to these antigens in either of the assays, and background in antigen-free controls was generally low. These results indicate that measurement of IFN-gamma by the ELISPOT assay or ELISA should have wide applications in large-scale epidemiological studies of malaria immunity. In addition, the ELISPOT assay makes it possible to analyze the T cells responding to malarial antigens in terms of both numbers and functional heterogeneity.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/iai.58.9.2989-2994.1990
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1990
    detail.hit.zdb_id: 1483247-1
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  • 6
    Online Resource
    Online Resource
    Novel proteins of Plasmodium falciparum identified by differential immunoscreening using immune and patient sera
    American Society for Microbiology ; 1994
    In:  Infection and Immunity Vol. 62, No. 2 ( 1994-02), p. 651-656
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 62, No. 2 ( 1994-02), p. 651-656
    Abstract: A differential serological screen of a lambda gt11 cDNA expression library of Plasmodium falciparum was performed in an attempt to identify novel and putative host-protective antigens of the parasite. The screening was done with two categories of sera: (i) acute-phase sera obtained from smear-positive acutely infected P. falciparum patients from various regions in India and (ii) immune sera taken from healthy, permanent adult residents of P. falciparum-endemic rural districts of Orissa in eastern India. These adults had not suffered from any clinical malarial symptoms for at least the previous 3 years at the time of serum collection. Sixty-five clones obtained by screening the lambda gt11 library with two immune serum samples were analyzed extensively with a total of 70 acutely infected patient serum samples. Eight of these clones failed to react with any of the patient sera. Each of these eight clones, when tested individually with 92 serum samples from the immune group, reacted with a minimum of 43% of the samples from this category of sera. Thus, these eight epitopes may encode host-protective elements since they are not recognized by antibodies in the patient sera but react exclusively and extensively with the clinically immune set. Sequence analysis of two of these clones reveals that they are novel Plasmodium genes.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/iai.62.2.651-656.1994
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1994
    detail.hit.zdb_id: 1483247-1
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  • 7
    Online Resource
    Online Resource
    Production by activated human T cells of interleukin 4 but not interferon-gamma is associated with elevated levels of serum antibodies to activating malaria antigens.
    Proceedings of the National Academy of Sciences ; 1990
    In:  Proceedings of the National Academy of Sciences Vol. 87, No. 14 ( 1990-07), p. 5484-5488
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 87, No. 14 ( 1990-07), p. 5484-5488
    Abstract: T cells play a crucial role in antibody-mediated and antibody-independent immunity against Plasmodium falciparum malaria. Therefore, a vaccine immunogen should include parasite-derived B- and T-cell epitopes capable of giving rise to protective responses in both systems. The P. falciparum antigen Pf155/ring-infected erythrocyte surface antigen (RESA), a vaccine candidate, contains immunodominant T- and B-cell epitopes located in the central (5') and C-terminal (3') invariant repeat regions of the molecule. To relate Pf155/RESA-peptide-specific responses of T cells to function, T cells from P. falciparum immune donors were activated with peptides corresponding to these immunodominant regions. Activation was measured as induction of interferon-gamma secretion, T-cell proliferation (DNA synthesis), or transcription and translation of interleukin 4 (IL-4) mRNA. Peptides from both regions were shown to induce interferon-gamma, IL-4, proliferation, or any combination. In individual donors, there was no correlation between these different activities. Rather, they were negatively correlated, demonstrating the importance of examining multiple parameters of T-cell activation when estimating the proportion of individuals responding to a given epitope. However, IL-4 mRNA and intracellular IL-4 could be induced in T cells of donors who had elevated concentrations of serum antibodies to the same peptide that was used for T-cell activation. These results suggest that a causal relationship exists between the activation of IL-4-producing T-cell subsets and production of the anti-Pf155/RESA-specific antibodies in individuals in which immunity has been induced by natural infection. This finding has implications that should be considered for the selection of immunogens to be included in a future P. falciparum subunit vaccine and for vaccine development in general.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.87.14.5484
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1990
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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