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Journal of Virology, September 1998, p. 7310-7319, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

DNA Vaccination Affords Significant Protection against Feline Immunodeficiency Virus Infection without Inducing Detectable Antiviral Antibodies

Margaret J. Hosie,* J. Norman Flynn, Mark A. Rigby, Celia Cannon, Thomas Dunsford, Nancy A. Mackay, David Argyle, Brian J. Willett, Takayuki Miyazawa,dagger David E. Onions, Oswald Jarrett, and James C. Neil

Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow, Bearsden, Glasgow G61 1QH, United Kingdom

Received 18 February 1998/Accepted 19 May 1998

To test the potential of a multigene DNA vaccine against lentivirus infection, we generated a defective mutant provirus of feline immunodeficiency virus (FIV) with an in-frame deletion in pol (FIVDelta RT). In a first experiment, FIVDelta RT DNA was administered intramuscularly to 10 animals, half of which also received feline gamma interferon (IFN-gamma ) DNA. The DNA was administered in four 100-µg doses at 0, 10, and 23 weeks. Immunization with FIVDelta RT elicited cytotoxic T-cell (CTL) responses to FIV Gag and Env in the absence of a serological response. After challenge with homologous virus at week 26, all 10 of the control animals became seropositive and viremic but 4 of the 10 vaccinates remained seronegative and virus free. Furthermore, quantitative virus isolation and quantitative PCR analysis of viral DNA in peripheral blood mononuclear cells revealed significantly lower virus loads in the FIVDelta RT vaccinates than in the controls. Immunization with FIVDelta RT in conjunction with IFN-gamma gave the highest proportion of protected cats, with only two of five vaccinates showing evidence of infection following challenge. In a second experiment involving two groups (FIVDelta RT plus IFN-gamma and IFN-gamma alone), the immunization schedule was reduced to 0, 4, and 8 weeks. Once again, CTL responses were seen prior to challenge in the absence of detectable antibodies. Two of five cats receiving the proviral DNA vaccine were protected against infection, with an overall reduction in virus load compared to the five infected controls. These findings demonstrate that DNA vaccination can elicit protection against lentivirus infection in the absence of a serological response and suggest the need to reconsider efficacy criteria for lentivirus vaccines.

* Corresponding author. Mailing address: Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow, Bearsden, Glasgow G61 1QH, United Kingdom. Phone: 44 141 330 3274. Fax: 44 141 330 5602. E-mail: m.hosie{at}vet.gla.ac.uk.

dagger Present address: Department of Veterinary Microbiology, Faculty of Agriculture, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.

Journal of Virology, September 1998, p. 7310-7319, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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