administration of exogenous cytokines may influence elicited immune responses, and hence may change the efficacy of a vaccine. We investigated the effects of tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-2 (IL-2) and interferon-γ (IFN-γ) on the immune response elicited by inactivated rabies virus vaccine in a mouse model. Each of the cytokines increased virus-specific IgG responses after primary and after secondary immunization. A single dose of 1.3 ng TNF-α or IL-1α, when injected shortly before vaccination, only marginally stimulated resistance to challenge infection (four- and seven-fold, respectively) without enhancing virus neutralizing antibody (VNAb) responses. In contrast, a single injection of 10 units of IFN-γ or five daily injections of 1.6 µg IL-2 increased vaccine dilutions protecting 50% of mice (PD values) 77- to 50-fold, respectively, with a concomitant enhancement of VNAb. At a 1:10000 dilution of a standard inactivated rabies vaccine preparation both IFN-γ and IL-2 increased protective immunity without enhancing VNAb responses; in non-vaccinated animals this treatment had no effect on resistance to challenge. Combined administration of IFN-γ and IL-2 synergistically enhanced VNAb responses. In contrast to the other cytokines tested, IFN-γ preferentially stimulated virus-specific IgG2a production. It also augmented the vaccine-induced priming of rabies virus-specific splenocyte proliferation. These results document that certain cytokines alone or in combination are potent immunological adjuvants which may direct and modulate immunization-induced antiviral immune responses.


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