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Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois

Requests for reprints: Liang Qiao, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153. Phone: 708-327-3481; Fax: 708-216-1196; E-mail: lqiao{at}lumc.edu.

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- 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.

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