In vivo 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-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) 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-alpha or IL-1 alpha, 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(3) units of IFN-gamma or five daily injections of 1.6 micrograms IL-2 increased vaccine dilutions protecting 50% of mice (PD50 values) 77- to 50-fold, respectively, with a concomitant enhancement of VNAb. At a 1:10,000 dilution of a standard inactivated rabies vaccine preparation both IFN-gamma 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-gamma and IL-2 synergistically enhanced VNAb responses. In contrast to the other cytokines tested, IFN-gamma 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.

Additional Metadata
Keywords 0 (Antibodies, Viral), 0 (Cytokines), 0 (Immunoglobulin G), 0 (Interleukin-1), 0 (Interleukin-2), 0 (Rabies Vaccines), 0 (Tumor Necrosis Factor), 0 (Vaccines, Inactivated), 82115-62-6 (Interferon Type II), Animals, Antibodies, Viral/*biosynthesis/blood/drug effects, Cell Division/drug effects, Cytokines/*pharmacology, Female, Immunoglobulin G/*biosynthesis/blood/drug effects, Interferon Type II/pharmacology, Interleukin-1/pharmacology, Interleukin-2/pharmacology, Male, Mice, Mice, Inbred C57BL, Neutralization Tests, Rabies Vaccines/*immunology, Spleen/cytology/drug effects, Support, Non-U.S. Gov't, Tumor Necrosis Factor/pharmacology, Vaccines, Inactivated/immunology
Persistent URL hdl.handle.net/1765/3484
Citation
Schijns, V.E.C.J., Claassen, I.J.Th.M., Vermeulen, A.A., Horzinek, M.C., & Osterhaus, A.D.M.E.. (1994). Modulation of antiviral immune responses by exogenous cytokines: effects of tumour necrosis factor-α interleukin-1 α, interleukin-2 and interferon-γ on the immunogenicity of an inactivated rabies vaccine.. Journal of General Virology, 75, 55–63. Retrieved from http://hdl.handle.net/1765/3484