OM-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic C-terminal fragment 242-310 from the circumsporozoite protein of Plasmodium berghei.
The goal of this project was the evaluation of a novel immunomodulatory adjuvant for human use, OM-174, which is a soluble adjuvant derived from Escherichia coli lipid A. For this study, we used a synthetic peptide, known for its safety and reproducibility and the murine model of BALB/c mice. The long peptide (PbCS 242-310) used corresponds to the C-terminal region of the circumsporozoite protein (CSP) that is the major protein on the surface of Plasmodium sporozoites. Subcutaneous injections of PbCS 242-310 in combination with soluble adjuvant OM-174 induced long lasting peptide-specific antibody titres comparable to those obtained by immunization with incomplete Freund's adjuvant (IFA). The ex vivo evaluation of the CD8(+) T cell response by IFN-gamma ELISPOT assay revealed that the injection of polypeptide with OM-174 adjuvant induced, compared to IFA, a similar and an eight-fold increased frequency of peptide-specific lymphocytes in the draining lymph-nodes and in the spleen, respectively. The CD8(+) T-cells are specific for the sequence PbCS 245-253, a well-known H-2K(d)-restricted CTL epitope, and are cytotoxic as shown in a chromium release assay. Immunization of BALB/c mice with this polypeptide in combination with adjuvant OM-174 conferred a protection after challenge with live Plasmodium berghei sporozoites.The strong antibody and CTL responses observed to a synthetic peptide in mice, the safety profile of the adjuvant and its extensive physico-chemical characterization suggest that OM-174 has a potential use in vaccine formulations for humans.
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Valentin
V
Meraldi
Régine
R
Audran
Jackeline F
JF
Romero
Vincent
V
Brossard
Jacques
J
Bauer
José Alejandro
JA
López
Giampietro
G
Corradin
D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008050:Lipid A; D008070:Lipopolysaccharides; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C400105:defoslimod