title: Murine immune responses to liver-stage antigen 1 protein FMP011, a malaria vaccine candidate, delivered with adjuvant AS01B or AS02A.
abstract: Liver-stage antigen 1 (LSA1) is expressed by Plasmodium falciparum only during the intrahepatic cell stage of the parasite's development. Immunoepidemiological studies in regions where malaria is endemic suggested an association between the level of LSA1-specific humoral and cell-mediated immune responses and susceptibility to clinical malaria. A recombinant LSA1 protein, FMP011, has been manufactured as a preerythrocytic vaccine to induce an immune response that would have the effect of controlling parasitemia and disease in humans. To evaluate the immunogenicity of FMP011, we analyzed the immune response of three inbred strains of mice to antigen immunization using two different adjuvant formulations, AS01B and AS02A. We report here the ability of BALB/c and A/J mice, but not C57BL/6J mice, to mount FMP011-specific humoral (antibody titer) and cellular (gamma interferon [IFN-gamma] production) responses following immunization with FMP011 formulated in AS01B or AS02A. Immunization of BALB/c and A/J mice with FMP011/AS01B induced more antigen-specific IFN-gamma-producing splenocytes than immunization with FMP011/AS02A. A slightly higher titer of antibody was induced using AS02A than AS01B in both strains. C57BL/6J mice did not respond with any detectable FMP011-specific IFN-gamma splenocytes or antibody when immunized with FMP011 in AS01B or AS02A. Intracellular staining of cells isolated from FMP011/AS01B-immunized BALB/c mice indicated that CD4(+) cells, but not CD8(+) cells, were the main IFN-gamma-producing splenocyte. However, inclusion of blocking anti-CD4(+) antibody during the in vitro restimulation ELISpot analysis failed to completely abolish IFN-gamma production, indicating that while CD4(+) T cells were the major source of IFN-gamma, other cell types also were involved.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, USA.
authors.forename: Clara
authors.initials: C
authors.lastname: Brando
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ware
authors.forename: Helen
authors.initials: H
authors.lastname: Freyberger
authors.forename: April
authors.initials: A
authors.lastname: Kathcart
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Barbosa
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cayphas
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitie
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C067302:liver stage-specific antigen, Plasmodium; D007371:Interferon-gamma