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

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 replicationdefective 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.

AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine

“…As expected for a virulent virus such as GL8 (30,31), in spite of the smaller dose inoculated, replication of the challenge virus in naive cats was more florid than that observed with the vaccine virus. Plasma viremia peaked at levels that ranged between 18,240 and 31,100 copies per ml at 1 month postchallenge (p.c.)…”

Dynamics of Viral and Proviral Loads of FelineImmunodeficiency Virus within the Feline Central Nervous System duringthe Acute Phase following IntravenousInfection

“…FIV GL8 is a primary isolate that has been passaged minimally in feline T cells (32). In contrast to the prototypic Petaluma strain isolated (FIVPET), FIV GL8 has a limited in vivo cell host range that does not extend to the CrFK cell line (33), and it is virulent in vivo, leading to high viral loads in plasma (35).…”

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

“…All three cats were chronically infected. Virus were isolated by cultivation of the cats' PBMC [14]. PBMCs were fractionated from 5 ml of heparinised whole blood by centrifugation over a Ficoll-Paque solution with a density of 1.077 g/ml.…”