Evaluation of feline immunodeficiency virus ORF-A mutants as candidate attenuated vaccine

Feline immunodeficiency virus (FIV) made defective in the accessory gene ORF-A were previously shown to be greatly attenuated in its ability to replicate in lymphocytes but to grow normally or near normally in other cell types. Here, we examined whether FIV thus mutated could protect specific pathogen-free cats against challenge with ex vivo fully virulent homologous virus. No reversion of the vaccinating infections to wild type ORF-A was noted over 22 months of in vivo infection. Following challenge, 6/6 unvaccinated control cats became readily and heavily infected. In contrast, 3/9 vaccinees showed no evidence of the challenge virus over a 15-month observation period. In the other vaccinees, the challenge virus was predominant for various periods of time, but pre-existing viral loads and CD4 lymphocyte counts were either unaffected or altered only marginally and transiently. These findings show that ORF-A-defective FIV should be further examined as a candidate live attenuated vaccine.