Enhancement of the protective effect of inactivated influenza virus vaccine by cytokines.

The authors examined whether or not cytokines in conjunction with inactivated influenza virus vaccine enhance protection from influenza virus infection in mice. Mice were infected with influenza virus A/PR/8/34 (PR/8) at 10 LD50 by nebulizer after intranasal administration of the cytokine and the vaccine. The survival rate of the group which received both the vaccine and mouse recombinant interferon-beta (MuIFN-beta; 1 x 10(4) IU/mouse) or mouse recombinant interferon-gamma (MuIFN-gamma; 1 x 10(4) IU/mouse) was significantly higher than that of the control group given the vaccine alone. These results show that MuIFN-beta and MuIFN-gamma have an adjuvant effect on this vaccination. In contrast, human recombinant interleukin-2 (HuIL-2) and human recombinant tumour necrosis factor (HuTNF) did not have an adjuvant effect. In order to examine the mechanism of the enhancing effect of MuIFN-gamma on this vaccination, we determined the specific IgA and IgG antibodies present in bronchoalveolar lavage fluid (BALF) and serum, and haemagglutination inhibition (HI) antibody in serum. In the early stage of infection, the titres of IgA and IgG antibodies in the combined group receiving the vaccine with MuIFN-gamma showed a tendency to be higher than those in the group given the vaccine alone. In the late stage of infection, the titre of HI antibody in the group given the vaccine with MuIFN-gamma was significantly lower than that in the group given vaccine alone. It can be concluded from these results that a part of the adjuvant effect of MuIFN-gamma on this vaccination was due to an increase in production of antibodies which neutralized the virus in the lesion.