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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,
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 (FIV
RT). In a first experiment, FIV
RT DNA was
administered intramuscularly to 10 animals, half of which also received
feline gamma interferon (IFN-
) DNA. The DNA was
administered in four 100-µg doses at 0, 10, and 23 weeks.
Immunization with FIV
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 FIV
RT vaccinates than in the controls.
Immunization with FIV
RT in conjunction with IFN-
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 (FIV
RT plus IFN-
and IFN-
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.

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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