The search for a safe vaccine that will confer significant protective immunity against the feline immunodeficiency virus (FIV) in cats is motivated by both concern for feline health and welfare as well as the desire to produce a safe and efficacious vaccine for the human immunodeficiency virus (HIV), also a lentivirus with genetic similarities to FIV. Utilizing receptor-mediated entry to cells, both FIV and HIV infect and replicate within CD4+ T cells, ultimately causing depletion of these cells, and result in similar immunopathogenic syndromes in infected individuals.
The currently available commercial FIV vaccine contains inactivated dual subtype (A and D) FIV-infected cells, and its efficacy and usefulness is controversial. Future development of both FIV and HIV vaccines needs to focus on development of protective anti-immunodeficiency virus T cell immunity rather than anti-immunodeficiency virus antibody.
CD134 is the primary binding receptor for FIV on target cells, and when the virus binds to this receptor, its envelope surface glycoprotein gp95 (SU) alters its conformation so that high affinity binding with the T cell surface entry receptor CXCR4 takes place. A very similar process takes place when HIV infects human T cells. The FIV SU therefore is an important target for induction of neutralizing antibodies. On the T cell surface, autoantibodies to the CD134 receptor have the potential to block infection.
The goal of this study was to determine whether vaccination of cats with CD134-SU complexes would be protective against FIV infection. Fifteen specific pathogen free (SPF) 8-11 week old cats were enrolled in one vaccine protocol (Vaccine Protocol I), while 12 SPF 8-11 week old cats were enrolled in Vaccine Protocol II. In Protocol I, cats were immunized with recombinant FIV-SU protein (derived by expression and purification from Chinese hamster ovary cells) alone or a complex of recombinant FIV-SU protein with soluble CD134. In Protocol 2, cats were immunized with soluble CD134, recombinant FIV-SU protein derived by expression and purification from human cells, or both together as a complex.
Immunization of the cats proved successful in that the cats produced anti-CD134 and anti-SU antibodies, and these antibodies significantly inhibited FIV infection in vitro. However, when the cats were challenged with actual FIV infection, no vaccine combination was protective, and serum from the vaccinated cats actually enhanced FIV growth in vitro. The investigators concluded that heat-labile factors, including complement, in the serum of vaccinates, may reduce the activity of anti-receptor antibody complexes and enhance viral replication, thereby impacting vaccine efficacy. Also, changes in circulating target cell populations, possibly with enhanced susceptibility to FIV infection, induced by the vaccination itself, may also be a factor in vaccine failure. [PJS]