Summary auto-generated
Researchers vaccinated cats with fixed autologous feline immunodeficiency virus (FIV)-infected cells to present viral proteins to individual cats in a major histocompatibility complex (MHC)-matched manner. While the vaccination successfully induced Gag-specific antibodies and virus-neutralizing antibodies in some assay systems, vaccinated cats were not protected against challenge infection. Instead, vaccinated cats developed accelerated viral replication compared to control cats in the early weeks following challenge with the homologous molecular clone FIV-19k1. Vaccinated cats showed detectable proviral DNA and infected cells at 2 weeks post-challenge, whereas unvaccinated controls showed these markers at 4 weeks post-challenge. By 6 weeks post-challenge, virus loads became equivalent between groups. The researchers investigated whether antibodies caused this enhancement by transferring plasma or purified immunoglobulins to naive kittens; however, no enhancement was observed. The findings demonstrate that vaccine-induced enhancement of lentivirus infection remains a significant complication in FIV vaccine development, likely involving multiple mechanisms including virus phenotype and cellular responses.
Key findings
- Vaccination with fixed autologous FIV-infected cells induced Gag-specific antibodies and neutralizing antibodies in cell culture-based assays, but failed to protect cats against homologous challenge infection.
- Vaccinated cats exhibited accelerated virus replication compared to unvaccinated controls, with proviral DNA and infected cells appearing 2 weeks earlier post-challenge in vaccinated animals.
- Vaccine-induced enhancement of infection could not be transferred to naive kittens by plasma or purified immunoglobulins from vaccinated cats, suggesting antibodies alone were insufficient to cause the enhancement.
- Enhancement of lentivirus infections represents a major obstacle in vaccine development, potentially involving virus phenotype, immune activation, and cytokine-mediated mechanisms beyond simple antibody-mediated enhancement.
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Abstract
Cats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore, virus-neutralizing antibodies were detected in a Crandell feline kidney cell-based neutralization assay, but not in a neutralization assay based on primary peripheral blood mononuclear cells. Despite the induction of these FIV-specific responses, vaccinated cats were not protected. Instead, accelerated virus replication was found, an observation similar to what previous experiments using other vaccine candidates have shown. Here, the results of the present study are discussed in the light of enhancement of lentivirus infections as a complicating factor in lentivirus vaccine development.