AIDS vaccination studies using an ex vivo feline immunodeficiency virus model: failure to protect and possible enhancement of challenge infection by four cell-based vaccines prepared with autologous lymphoblasts.
AIDS vaccination studies using an ex vivo feline
immunodeficiency virus model: failure to protect and possible enhancement of
challenge infection by four cell-based vaccines prepared with autologous
lymphoblasts.
Giannecchini S, Isola P, Sichi O, Matteucci D, Pistello M, Zaccaro L, Del
Mauro D, Bendinelli M.
Retrovirus Center and Virology Section, Department of Biomedicine, University of
Pisa, Pisa, Italy.
Immunogenicity and protective activity of four cell-based feline
immunodeficiency virus (FIV) vaccines prepared with autologous lymphoblasts were
investigated. One vaccine was composed of FIV-infected cells that were
paraformaldehyde fixed at the peak of viral expression. The other vaccines were
attempts to maximize the expression of protective epitopes that might become
exposed as a result of virion binding to cells and essentially consisted of
cells mildly fixed after saturation of their surface with adsorbed, internally
inactivated FIV particles. The levels of FIV-specific lymphoproliferation
exhibited by the vaccinees were comparable to the ones previously observed in
vaccine-protected cats, but antibodies were largely directed to cell-derived
constituents rather than to truly viral epitopes and had very poor FIV-neutralizing
activity. Moreover, under one condition of testing, some vaccine sera enhanced
FIV replication in vitro. As a further limit, the vaccines proved inefficient at
priming animals for anamnestic immune responses. Two months after completion of
primary immunization, the animals were challenged with a low dose of homologous
ex vivo FIV. Collectively, 8 of 20
vaccinees
developed infection versus one of nine animals mock immunized with fixed
uninfected autologouslymphoblasts.
After a boosting and rechallenge
with a higher virus dose, all remaining animals became infected, thus confirming
their lack of protection.
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