Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909.

Détails

ID Serval
serval:BIB_1F6FBB6665E9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909.
Périodique
Journal of Clinical Investigation
Auteur(s)
Speiser D.E., Liénard D., Rufer N., Rubio-Godoy V., Rimoldi D., Lejeune F., Krieg A.M., Cerottini J.C., Romero P.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
115
Numéro
3
Pages
739-746
Langue
anglais
Notes
Publication types: Clinical Trial ; Clinical Trial, Phase I ; Journal Article
Résumé
The induction of potent CD8+ T cell responses by vaccines to fight microbes or tumors remains a major challenge, as many candidates for human vaccines have proved to be poorly immunogenic. Deoxycytidyl-deoxyguanosin oligodeoxynucleotides (CpG ODNs) trigger Toll-like receptor 9, resulting in dendritic cell maturation that can enhance immunogenicity of peptide-based vaccines in mice. We tested whether a synthetic ODN, CpG 7909, could improve human tumor antigen-specific CD8+ T cell responses. Eight HLA-A2+ melanoma patients received 4 monthly vaccinations of low-dose CpG 7909 mixed with melanoma antigen A (Melan-A; identical to MART-1) analog peptide and incomplete Freund's adjuvant. All patients exhibited rapid and strong antigen-specific T cell responses: the frequency of Melan-A-specific T cells reached over 3% of circulating CD8+ T cells. This was one order of magnitude higher than the frequency seen in 8 control patients treated similarly but without CpG and 1-3 orders of magnitude higher than that seen in previous studies with synthetic vaccines. The enhanced T cell populations consisted primarily of effector memory cells, which in part secreted IFN- and expressed granzyme B and perforin ex vivo. In vitro, T cell clones recognized and killed melanoma cells in an antigen-specific manner. Thus, CpG 7909 is an efficient vaccine adjuvant that promotes strong antigen-specific CD8+ T cell responses in humans.
Mots-clé
Animals, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Freund's Adjuvant, HLA-A2 Antigen, Humans, Interferon-gamma, Lipids, Lymphocyte Activation, Melanoma, Neoplasm Proteins, Oligodeoxyribonucleotides, Quality Control, Vaccination
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:14
Dernière modification de la notice
20/08/2019 12:55
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