Mice lacking the transcription factor subunit Rel can clear an influenza infection and have functional anti-viral cytotoxic T cells but do not develop an optimal antibody response.

Rel, a haemopoietic cell-restricted member of the NF-kappaB/Rel family of transcription factors, has recently been shown to be important in the function of B and T lymphocytes. In an attempt to understand the role of this protein in the immune response, we examined the ability of Rel(-/-) mice to counter an influenza virus infection. Normal levels of virus-specific cytotoxic T cells induced in Rel(-/-) mice were able to clear virus from the lungs, albeit with somewhat delayed kinetics compared to normal mice. Rel(-/-) mice did, however, display a markedly reduced T cell proliferative response to the virus, and exhibited impaired local and systemic influenza virus-specific antibody responses. This defect was sufficient to result in an inability of vaccinated mice, but not of previously infected mice, to acquire antibody-dependent protective immunity to reinfection with the same virus. These findings establish that during the response to influenza virus, Rel function allows optimal development of humoral immunity, a role that apparently cannot be fulfilled by other NF-kappaB/Rel proteins.

Immunopotentiation of humoral and cellular responses to inactivated influenza vaccines by two different adjuvants with potential for human use.

Two quite different adjuvants, currently under development for use in humans, have been examined for their effects on the magnitude and type of immunity elicited in response to inactivated influenza vaccine. Immunostimulating complexes (ISCOM adjuvant) contain the saponin ISCOPREP 703, and SPT is an oil-in-water emulsion of squalane, non-ionic block copolymer (L121) and Tween 80. Influenza virus vaccines formulated in either adjuvant were far superior to the non-adjuvanted aqueous vaccine in eliciting antibody and T-cell responses in mice, particularly at lower doses of antigen. In addition, the vaccines containing adjuvant were superior in eliciting protective immunity. One of the shortcomings of the unadjuvanted inactivated influenza vaccine was its inability to elicit a primary proliferative T-cell response. However, after one dose of either adjuvanted vaccine, strong proliferative responses were achieved. We also show that subcutaneous vaccination with inactivated vaccines is capable of modulating the isotype profile of antibody secreting cells generated in the lungs of mice in response to intranasal challenge with live virus. In this system, the isotype of antibody elicited after challenge of mice that had received ISCOM vaccine more closely mimicked that of animals vaccinated with live virus.