title: Characterization of conserved T- and B-cell epitopes in Plasmodium falciparum major merozoite surface protein 1.
abstract: Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMILNEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria.
authors.affiliation: Departments of Biology, Georgetown University, Washington, DC 20057, USA. Parram@gusun.georgetown.edu
authors.forename: M
authors.initials: M
authors.lastname: Parra
authors.forename: G
authors.initials: G
authors.lastname: Hui
authors.forename: A H
authors.initials: AH
authors.lastname: Johnson
authors.forename: J A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: T
authors.initials: T
authors.lastname: Roberts
authors.forename: I A
authors.initials: IA
authors.lastname: Quakyi
authors.forename: D W
authors.initials: DW
authors.lastname: Taylor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D002455:Cell Division; D017124:Conserved Sequence / Q000276:immunology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D020066:Merozoite Surface Protein 1; D010455:Peptides; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic