Feline leukaemia virus (FeLV) is a pathogen inducing fatal disease in cats worldwide. By applying sensitive molecular assays, efficacious commonly used FeLV vaccines that protect cats from antigenaemia were found not to prevent proviral integration and minimal viral replication after challenge. Nonetheless, vaccines protected cats from FeLV-associated disease and prolonged life expectancy. The spectrum of host response categories was refined by investigating plasma viral RNA loads. All cats initially fought similar virus loads, although subsequently loads were associated with infection outcomes. Persistence of plasma viral RNA was moderately associated with reactivation of FeLV infection. In conclusion, sensitive molecular assays are important tools for reviewing pathogenesis of FeLV infection.