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Journal of Virology, July 2002, p. 6882-6892, Vol. 76, No. 14
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.14.6882-6892.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Failure To Protect and Possible Enhancement of Challenge Infection by Four Cell-Based Vaccines Prepared with Autologous Lymphoblasts
Simone Giannecchini, Patrizia Isola, Olimpia Sichi, Donatella Matteucci, Mauro Pistello, Lucia Zaccaro, Daniela Del Mauro, and Mauro Bendinelli*
Retrovirus Center and Virology Section, Department of Biomedicine, University of Pisa, Pisa, Italy
Received 7 February 2002/
Accepted 15 April 2002
Immunogenicity and protective activity of four cell-based feline immunodeficiency virus (FIV) vaccines prepared with autologous lymphoblasts were investigated. One vaccine was composed of FIV-infected cells that were paraformaldehyde fixed at the peak of viral expression. The other vaccines were attempts to maximize the expression of protective epitopes that might become exposed as a result of virion binding to cells and essentially consisted of cells mildly fixed after saturation of their surface with adsorbed, internally inactivated FIV particles. The levels of FIV-specific lymphoproliferation exhibited by the vaccinees were comparable to the ones previously observed in vaccine-protected cats, but antibodies were largely directed to cell-derived constituents rather than to truly viral epitopes and had very poor FIV-neutralizing activity. Moreover, under one condition of testing, some vaccine sera enhanced FIV replication in vitro. As a further limit, the vaccines proved inefficient at priming animals for anamnestic immune responses. Two months after completion of primary immunization, the animals were challenged with a low dose of homologous ex vivo FIV. Collectively, 8 of 20 vaccinees developed infection versus one of nine animals mock immunized with fixed uninfected autologous lymphoblasts. After a boosting and rechallenge with a higher virus dose, all remaining animals became infected, thus confirming their lack of protection.
* Corresponding author. Mailing address: Dipartimento di Biomedicina, Università di Pisa, Via San Zeno 37, I-56127 Pisa, Italy. Phone: 39-050-553562. Fax: 39-050-559455. E-mail: bendinelli{at}biomed.unipi.it.
Journal of Virology, July 2002, p. 6882-6892, Vol. 76, No. 14
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.14.6882-6892.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.