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An HLA-A2.1-Transgenic Rabbit Model to Study Immunity to Papillomavirus Infection¹

Jiafen Hu^*,, Xuwen Peng, Todd D. Schell, Lynn R. Budgeon^*,, Nancy M. Cladel^*, and Neil D. Christensen^2,*,,

^* Jake Gittlen Cancer Research Foundation, Department of Pathology, Department of Microbiology and Immunology, and Department of Comparative Medicine, College of Medicine, Pennsylvania State University, Hershey, PA 17033

We have established several HLA-A2.1-transgenic rabbit lines to provide a host to study CD8⁺ T cell responses during virus infections. HLA-A2.1 protein expression was detected on cell surfaces within various organ tissues. Continuous cultured cells from these transgenic rabbits were capable of presenting both endogenous and exogenous HLA-A2.1-restricted epitopes to an HLA-A2.1-restricted epitope-specific CTL clone. A DNA vaccine containing an HLA-A2.1-restricted human papillomavirus type 16 E7 epitope (amino acid residues 82–90) stimulated epitope-specific CTLs in both PBLs and spleen cells of transgenic rabbits. In addition, vaccinated transgenic rabbits were protected against infection with a mutant cottontail rabbit papillomavirus DNA containing an embedded human papillomavirus type 16 E7/82–90 epitope. Complete protection was achieved using a multivalent epitope DNA vaccine based on epitope selection from cottontail rabbit papillomavirus E1 using MHC class I epitope prediction software. HLA-A2.1-transgenic rabbits will be an important preclinical animal model system to study virus-host interactions and to assess specific targets for immunotherapy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Public Health Service, National Cancer Institute Grant R01 CA47622 from the National Institutes of Health, and the Jake Gittlen Memorial Golf Tournament.

² Address correspondence and reprint requests to Dr. Neil D. Christensen, Pennsylvania State University, Hershey, PA 17033. E-mail address: ndc1{at}psu.edu

³ Abbreviations used in this paper: HPV, human papillomavirus; VLP, virus-like particle; CRPV, cottontail rabbit papillomavirus; MHCI, MHC class I; MFI, mean fluorescence intensity.

This article has been cited by other articles:

				J. Hu, X. Peng, L. R. Budgeon, N. M. Cladel, K. K. Balogh, and N. D. Christensen Establishment of a Cottontail Rabbit Papillomavirus/HLA-A2.1 Transgenic Rabbit Model J. Virol., July 1, 2007; 81(13): 7171 - 7177. [Abstract] [Full Text] [PDF]