title: Influence of adjuvants in inducing immune responses to different epitopes included in a multiepitope, multivalent, multistage Plasmodium falciparum candidate vaccine (FALVAC-1) in outbred mice.
abstract: FALVAC-1, a vaccine against Plasmodium falciparum was developed by joining 21 epitopes from P. falciparum vaccine antigens and an universal T helper epitope from tetanus toxoid. Since adjuvants influence different aspects of immune responses, in this study we investigated the effect of four adjuvants aluminum hydroxide (alum), nonionic copolymer adjuvant P1005 (water-in-oil emulsion), CpG oligodeoxynucleotides (ODN), and QS-21 in eliciting immune responses in outbred mice. QS-21 and copolymer adjuvants were the best formulations in inducing higher and long-lasting antibody titers to the whole vaccine compared to alum and CpG. QS-21 was the only adjuvant to elicit predominantly IgG2a response and antibodies reactive with all epitopes incorporated in the vaccine construct. Vaccine elicited antibodies recognized sporozoites and asexual blood-stage parasites. FALVAC-1 immunized mice induced lymphoproliferative and IFN-gamma response to the vaccine. QS-21 and CpG adjuvants were able to elicit T proliferative responses to 20 of the 22 epitopes in the vaccine. In conclusion, this study demonstrated that with suitable adjuvant such as QS-21, it is possible to elicit immune responses to most of the epitopes included in the FALVAC-1 vaccine.
authors.affiliation: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop F-12, Atlanta, GA 30341, USA.
authors.forename: Asimah
authors.initials: A
authors.lastname: Rafi-Janajreh
authors.forename: Jon Eric
authors.initials: JE
authors.lastname: Tongren
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kensil
authors.forename: Craig
authors.initials: C
authors.lastname: Hackett
authors.forename: Francisco
authors.initials: F
authors.lastname: Candal
authors.forename: Altaf
authors.initials: A
authors.lastname: Lal
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
mesh_terms: D000276:Adjuvants, Immunologic / Q000592:standards*; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D000939:Epitopes; D007106:Immune Sera; D007074:Immunoglobulin G; D017780:Malaria Vaccines