FIV vaccine with receptor epitopes results in neutralizing antibodies but does not confer resistance to challenge

Abstract

Feline immunodeficiency virus (FIV) is the feline analogue to human immunodeficiency virus (HIV) and utilizes parallel modes of receptor-mediated entry. The FIV surface glycoprotein (SU) is an important target for induction of neutralizing antibodies, and autoantibodies to the FIV binding receptor (CD134) block infection ex vivo; thus highlighting the potential for immunotherapies which utilize anti-receptor antibodies to block viral infection. To determine whether vaccination with CD134-SU complexes could induce protection against FIV infection, cats ( n = 5 per group) were immunized with soluble CD134, recombinant FIV-SU protein, and/or CD134+SU complexes. Two trials were performed with different antigen combinations and vaccination schedules. In vivo generation of anti-CD134 and anti-SU IgG antibodies was measured, and in vitro neutralization assays were conducted. Immunization induced production of anti-CD134 and anti-SU antibodies that significantly inhibited FIV infection in vitro. However, no vaccine combination protected cats from FIV infection, and neat serum from vaccinated cats enhanced FIV growth in vitro. CD134+SU vaccinated cats exhibited increased CD4:CD8 ratio immediately prior to challenge, and antibodies were much more efficiently generated against vaccine by-products versus target antigens. Results suggest vaccination against viral and cryptic receptor epitopes yields neutralizing antibodies that synergistically inhibit FIV infection in vitro. Factors contributing to vaccine failure may include: (1) Heat-labile serum factors that enhance viral replication, (2) changes in circulating target cell populations induced by vaccination, and (3) weak immunogenicity of neutralizing epitopes compared to off-target vaccine components. Results reinforce the need to monitor vaccine preparation components and avoid non-specific immune stimulation during vaccination.

Feline immunodeficiency virus: In vivo protection remains elusive

A vaccine candidate for feline immunodeficiency virus elicits strong immunological reaction in vitro, but no protection to live cats. The feline analog to human immunodeficiency virus, FIV shares a similar infection paradigm and has only one partially effective vaccine. A US team, led by Colorado State University’s Susan VandeWoude, immunized cats using a complex of an FIV surface protein and a feline cell-surface protein known to facilitate FIV’s entry into immune cells. Tissue culture assays yielded promising results; however, this did not translate to live-animal protection. The researchers highlighted multiple factors that could explain the lack of success, including circulatory pro-infection factors, and immune responses generated against vaccine by-products rather than intended targets. While the vaccine candidate failed, the research provides invaluable guidance for future efforts into FIV vaccination with implications for HIV vaccine trials.