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
Détails
ID Serval
serval:BIB_8FB8D9C81247
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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
Périodique
Vaccine
ISSN
0264-410X (Print)
Statut éditorial
Publié
Date de publication
06/2003
Volume
21
Numéro
19-20
Pages
2485-91
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun 2
Research Support, Non-U.S. Gov't --- Old month value: Jun 2
Résumé
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.
Mots-clé
Adjuvants, Immunologic
Animals
Antibodies, Protozoan/blood
Antigens, Protozoan/chemistry/*immunology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Humans
Lipid A/*immunology
Lipopolysaccharides/*immunology
Malaria/*immunology
Malaria Vaccines/*immunology
Mice
Mice, Inbred BALB C
Peptide Fragments/administration & dosage/*immunology
Plasmodium berghei/*immunology
Protozoan Proteins/chemistry/*immunology
Pubmed
Web of science
Création de la notice
24/01/2008 14:55
Dernière modification de la notice
20/08/2019 14:53