Antibodies specific for hypervariable regions 3 to 5 of the feline immunodeficiency virus envelope glycoprotein are not solely responsible for vaccine-induced acceleration of challenge infection in cats

Abstract

In a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a causative role for antibodies directed against the hypervariable regions HV3, HV4 and HV5 (HV3–5) of the envelope glycoprotein. The present study was designed to investigate further the contribution of antibodies in envelope vaccine-induced acceleration of FIV infection. To this end, regions HV3–5 of the envelope glycoprotein were deleted from the original vaccine, thus addressing the contributing role of antibodies directed against these hypervariable regions. Interestingly, this approach did not prevent acceleration of challenge infection. Analysis of the antibody responses in the respective groups suggested that removal of HV3–5 redirected the humoral immune response towards other regions of the envelope glycoprotein, indicating that these regions can also induce antibodies that accelerate virus replication.

Antibodies Generated in Cats by a Lipopeptide Reproducing the Membrane-Proximal External Region of the Feline Immunodeficiency Virus Transmembrane Enhance Virus Infectivity

“…Although we have no evidence that the effect observed is relevant in vivo, an enhancing or accelerating effect on FIV replication has been described for several situations, including vaccine experiments using immunogens of varied complexity, in which the factors responsible have most often eluded a clear identification (18,21,24,28,45,51). The enhancing effect described here was instead clearly characterized as mediated by the antibodies generated by lipo-P59, since it was reproduced by IgG and Fab purified from the sera and was ablated by preadsorption with lipo-P59.…”

Vaccine-induced enhancement of viral infections

“…In particular antibodies to the V3-V6 regions of the envelope protein were associated with the observed enhancement of infection. In a follow-up study, recombinant envelope protein was prepared from which the part encompassing the region between V3 and V6 was deleted [98]. Vaccination with this engineered protein still predisposed for increased susceptibility to infection and it was concluded that also antibodies directed to epitopes outside the V3-V6 region were able to cause enhancement of infection.…”

Feline Immunodeficiency Virus (FIV) Neutralization: A Review

“…Intriguingly, using a T cell based neutralization assay based on MBM cells (an IL2-dependent cell line similar to MYA-1 cells [88]), the sera from the immunized cats were found to enhance FIV infection, an effect that could be adsorbed by pre-incubation with lipo-P59 [87]. While disappointing from a vaccine design perspective, these findings may prove informative in interpreting why some FIV vaccines that failed to induce protective immunity, appeared to enhance infection following challenge [62,69,89–93]. …”