Branched and linear lipopeptide vaccines have different effects on primary CD4+ and CD8+ T-cell activation but induce similar tumor-protective memory CD8+ T-cell responses.
We compared murine T-cell responses to synthetic lipopeptide vaccines in which the TLR2 ligand Pam(2)Cys was attached to co-linear CD4+ and CD8+ T-cell epitopes of ovalbumin (OVA) in a linear or branched configuration. Mice received OVA-specific transgenic CD8+ and CD4+ T-cells followed by one injection of vaccine. Although the branched lipopeptide was more potent in activating OVA-specific CD4+ and CD8+ T-cells in the primary response, both vaccines induced cytolytic T lymphocytes (CTL) that expressed perforin, granzyme A-C, and IFN-gamma mRNAs and conferred long-term protection of most mice against challenge with OVA-expressing tumor cells. OVA epitope display was reduced in tumors that developed in some mice, suggesting CD8+ T-cell dependent selection.
Baz
Adriana
A
Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Queensland 4029, Australia.
Buttigieg
Kathy
K
Zeng
Weiguang
W
Rizkalla
Michael
M
Jackson
David C
DC
Groves
Penny
P
Kelso
Anne
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015870:Gene Expression; D053804:Granzymes / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D054353:Perforin / Q000096:biosynthesis; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
D019496:Cancer Vaccines; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D008074:Lipoproteins; C499841:PAM2-Cys-SKKK; D022223:Vaccines, Subunit; D054353:Perforin; D007371:Interferon-gamma; D010047:Ovalbumin; D053804:Granzymes