Dual-subtype FIV vaccine protects cats against in vivo swarms of both homologous and heterologous subtype FIV isolates

Objective: To evaluate the immunogenicity and efficacy of an inactivated du al-subtype feline immunodeficiency virus (FIV) vaccine. Design: Specific-pathogen-free cats were immunized with dual-subtype (subty pe A FIVPet and subtype D FIVShi) vaccine and challenged with either in viv o- or in vitro-derived FIV inocula. Methods: Dual-subtype vaccinated, single-subtype vaccinated, and placebo-im munized cats were challenged with in vivo-derived heterologous subtype B FI VBang [10-100 50% cat infectious doses (CID50)], in vivo-derived homologous FIVShi(50 CID50), and in vitro- and in vivo-derived homologous FIVPet(20-5 0 CID50). Dual-subtype vaccine immunogenicity and efficacy were evaluated a nd compared to single-subtype strain vaccines. FIV infection was determined using virus isolation and proviral PCR of peripheral blood mononuclear cel ls and lymphoid tissues. Results: Four out of five dual-subtype vaccinated cats were protected again st low-dose FIVBang (10 CID50) and subsequently against in vivo-derived FIV Pet (50 CID50) challenge, whereas all placebo-immunized cats became infecte d. Furthermore, dual-subtype vaccine protected two out of five cats against high-dose FIVBang challenge (100 CID50) which infected seven out of eight single-subtype vaccinated cats. All dual-subtype vaccinated cats were prote cted against in vivo-derived FIVPet but only one out of five single-subtype vaccinated cats were protected against in vivo-derived FIV(Pe)t. Dual-subt ype vaccination induced broad-spectrum virus-neutralizing anti bodies and F IV-specific interferon-gamma responses along with elevated FIV-specific per forin mRNA levels, suggesting an increase in cytotoxic cell activities. Conclusion: Dual-subtype vaccinated cats developed broad-spectrum humoral a nd cellular immunity which protected cats against in vivo-derived inocula o f homologous and heterologous FIV subtypes. Thus, multi-subtype antigen vac cines may be an effective strategy against AIDS viruses. (C) 2001 Lippincot t Williams & Wilkins.