Effects on immunogenicity by formulations of emulsion-based adjuvants for malaria vaccines.
New malaria vaccines are urgently needed to improve vaccine protective efficacy. PfCelTOS is a recombinant malaria vaccine antigen that has shown protective efficacy in a small-animal challenge model when combined with a water-in-oil emulsion adjuvant (Montanide ISA 720). In this report, we show that PfCelTOS vaccines containing GLA-SE (a stable oil-in-water emulsion combined with a Toll-like receptor 4 [TLR4] agonist) elicit strong Th1-type immune responses in BALB/c mice. These responses include higher antigen-specific IgG2a antibody titers and more gamma interferon (IFN-γ) production than those seen with a PfCelTOS vaccine containing Montanide ISA 720. Furthermore, reducing the emulsion dose from 2% to 1% or 0.5% (vol/vol) squalene in GLA-SE did not compromise immunogenicity. Emulsion dose titration in the absence of formulated GLA caused some reduction in humoral and cellular immune responses compared to those with the 2% squalene emulsion dose.
Infectious Disease Research Institute, Seattle, Washington, USA. cfox@idri.org
Christopher B
CB
Fox
Susan L
SL
Baldwin
Thomas S
TS
Vedvick
Evelina
E
Angov
Steven G
SG
Reed
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D004655:Emulsions; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008353:Mannitol / Q000031:analogs & derivatives / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009829:Oleic Acids / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D013185:Squalene; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004655:Emulsions; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D009829:Oleic Acids; D051197:Toll-Like Receptor 4; D014614:Vaccines, Synthetic; C001681:mannide monooleate; D008353:Mannitol; D013185:Squalene; D007371:Interferon-gamma