Induction of mucosal and systemic immune responses against human carcinoembryonic antigen by an oral vaccine.
Carcinoembryonic antigen (CEA) is a tumor-associated antigen targeted for the development of colorectal tumor vaccines. In this study, we developed papillomavirus pseudoviruses encoding the truncated CEA without NH2-terminal signal peptide (PV-CEA) as an oral vaccine to induce CEA-specific CTL responses. In CEA transgenic (CEA-Tg) mice orally immunized with PV-CEA, the immunologic tolerance to CEA as a "self-antigen" was overcome and both mucosal and systemic CEA-specific cytolytic activities were detected by in vitro 51Cr release assays. In a tumor prevention model, the growth rate of CEA+ tumors was significantly delayed in CEA-Tg mice orally immunized with PV-CEA when compared with the control vaccine. Further, the IFN-gamma enzyme-linked ImmunoSPOT and in vitro 51Cr release assay results showed that HLA-A2-restricted, CEA-specific CTL responses were induced in both mucosal and systemic lymphoid tissues in A2 transgenic mice after oral immunization with PV-CEA. Finally, we showed that coadministration of papillomavirus pseudoviruses encoding interleukin-2 with PV-CEA enhanced the generation of A2-restricted, CEA-specific CTLs in aged CEA/A2 double transgenic mice, which were more clinically relevant. Our data suggest that PV-CEA pseudovirus vaccine is a promising oral CEA vaccine for humans to induce CEA-specific CTLs at the site of colorectal tumors (i.e., intestinal mucosa), which might efficiently eliminate CEA+ colorectal tumor cells in the mucosa.
Huang
Yujun
Y
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Fayad
Raja
R
Smock
Andrew
A
Ullrich
Amanda M
AM
Qiao
Liang
L
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control; D000284:Administration, Oral; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000517:prevention & control; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D014765:Viral Vaccines