Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus

Abstract

ABSTRACT It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIV PET ) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIV AM6 and FIV GL8 . This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIV GL8 -infected cats. In contrast, DNA vaccines based on either FIV PET or FIV GL8 , which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIV PET but had no measurable effect on virus load when the infecting virus was FIV GL8 . These results indicate that the more virulent FIV GL8 is intrinsically more resistant to vaccinal immunity than the FIV PET strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.