title: Immune responses of mice with different genetic backgrounds to improved multiepitope, multitarget malaria vaccine candidate antigen FALVAC-1A.
abstract: FALVAC-1A is a second-generation multitarget, multiepitope synthetic candidate vaccine against Plasmodium falciparum, incorporating elements designed to yield a stable and immunogenic molecule. Characteristics of the immunogenicity of FALVAC-1A were evaluated in congenic (H-2(b), H-2(k), and H-2(d)) and outbred strains of mice. The influences of four adjuvants (aluminum phosphate, QS-21, Montanide ISA-720, and copolymer CRL-1005) on different aspects of the immune response were also assessed. FALVAC-1A generated strong antibody responses in all mouse strains. The highest mean enzyme-linked immunosorbent assay (ELISA) antibody concentrations against FALVAC-1A were observed in the outbred ICR mice, followed by B10.BR, B10.D2, and C57BL/6 mice, though this order varied for the different adjuvants, with no statistical differences between mouse strains. In all mouse strains, the highest anti-FALVAC-1A antibody titers in ELISAs were induced by FALVAC-1A in copolymer and ISA-720 formulations, followed by QS-21 and AlPO4. These antibodies were of all four subclasses, though immunoglobulin G1 (IgG1) predominated, with the exception of FALVAC-1A with the QS-21 adjuvant, which induced predominantly IgG2c responses. Both sporozoites and blood stages of P. falciparum were recognized by anti-FALVAC-1A sera in the immunofluorescence assay. In addition to antibody, cellular immune responses were detected; these responses were studied by examining spleen cells producing gamma interferon and interleukin-4 in enzyme-linked immunospot assays. In summary, FALVAC-1A was found to be highly immunogenic and elicited functionally relevant antibodies that can recognize sporozoites and blood-stage parasites in diverse genetic backgrounds.
authors.affiliation: Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Kaba
authors.forename: A
authors.initials: A
authors.lastname: Price
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: V
authors.initials: V
authors.lastname: Sundaram
authors.forename: P
authors.initials: P
authors.lastname: Schnake
authors.forename: I F
authors.initials: IF
authors.lastname: Goldman
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
authors.forename: V
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: C W
authors.initials: CW
authors.lastname: Todd
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010963:Plasmodium falciparum / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma
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