title: Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909.
abstract: 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.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. daniel.speiser@hospvd.ch.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Danielle
authors.initials: D
authors.lastname: Liénard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Verena
authors.initials: V
authors.lastname: Rubio-Godoy
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Ferdy
authors.initials: F
authors.lastname: Lejeune
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008055:Lipids / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology*; D011786:Quality Control; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D008055:Lipids; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; C483020:ProMune; C114843:incomplete Freund's adjuvant; D007371:Interferon-gamma; D005620:Freund's Adjuvant