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Journal of Virology, September 2006, p. 8856-8868, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00397-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

AIDS Vaccination Studies with an Ex Vivo Feline Immunodeficiency Virus Model: Analysis of the Accessory ORF-A Protein and DNA as Protective Immunogens

Mauro Pistello,1* Francesca Bonci,1 J. Norman Flynn,2,{dagger} Paola Mazzetti,1 Patrizia Isola,1 Elisa Zabogli,1 Valentina Camerini,1,3 Donatella Matteucci,1 Giulia Freer,1 Paolo Pelosi,4 and Mauro Bendinelli1

Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy,1 Department of Veterinary Pathology, University of Glasgow, Glasgow, United Kingdom,2 LaboRetro, INSERM U412, Ecole Normale Superieure de Lyon, Lyon, France,3 Department of Chemical and Agricultural Biotechnologies, University of Pisa, Pisa, Italy4

Received 24 February 2006/ Accepted 25 June 2006

Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All three immunization strategies used (protein alone in alum adjuvant, DNA alone, or DNA prime-protein boost) clearly generated detectable immune responses. Upon challenge with ex vivo homologous FIV, ORF-A-immunized cats showed distinct enhancement of acute-phase infection relative to mock-immunized animals given alum or empty vector DNA. This effect was tentatively attributed to increased expression of the FIV receptor CD134 that was observed in the immunized cats. However, at subsequent sampling points that were continued for up to 10 months postchallenge, the average plasma viral loads of the ORF-A-immunized animals were slightly but consistently reduced relative to those of the control animals. In addition, CD4+ T lymphocytes in the circulation system declined more slowly in immunized animals than in control animals. These findings support the contention that immunization with lentiviral accessory proteins can improve the host's ability to control virus replication and slow down disease progression but also draw attention to the fact that even simple immunogens that eventually contribute to protective activity can transiently exacerbate subsequent lentiviral infections.

* Corresponding author. Mailing address: Dipartimento di Patologia Sperimentale, Università di Pisa, Via San Zeno, 37, I-56127 Pisa, Italy. Phone: 39 050 221 3781. Fax: 39 050 221 3524. E-mail: pistello{at}biomed.unipi.it.

{dagger} Present address: P.O. Box 6779, Dundee DD1 9WN, Scotland.

Journal of Virology, September 2006, p. 8856-8868, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00397-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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