Optimized subunit vaccine protects against experimental leishmaniasis.
Development of a protective subunit vaccine against Leishmania spp. depends on antigens and adjuvants that induce appropriate immune responses. We evaluated a second generation polyprotein antigen (Leish-110f) in different adjuvant formulations for immunogenicity and protective efficacy against Leishmania spp. challenges. Vaccine-induced protection was associated with antibody and T cell responses to Leish-110f. CD4 T cells were the source of IFN-gamma, TNF, and IL-2 double- and triple-positive populations. This study establishes the immunogenicity and protective efficacy of the improved Leish-110f subunit vaccine antigen adjuvanted with natural (MPL-SE) or synthetic (EM005) Toll-like receptor 4 agonists.
Infectious Disease Research Institute, Seattle, WA 98104, USA. sbertholet@idri.org
Sylvie
S
Bertholet
Yasuyuki
Y
Goto
Lauren
L
Carter
Ajay
A
Bhatia
Randall F
RF
Howard
Darrick
D
Carter
Rhea N
RN
Coler
Thomas S
TS
Vedvick
Steven G
SG
Reed
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D054332:Leishmaniasis Vaccines; D011993:Recombinant Fusion Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; D007371:Interferon-gamma