The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and ≥3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV-1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy.