Recombinant adenovirus vectors expressing interleukin-5 and-6 specificallyenhance mucosal immunoglobulin A responses in the lung

In this study, we have examined the in vivo effects of interleukin-5 (IL-5) and IL-6 over-expression on systemic and mucosal immune responses using re combinant human type 5 adenoviruses capable of expressing these cytokines u pon infection. A recombinant adenovirus containing the murine IL-5 gene wit hin the E3 region was constructed and found to express high levels of IL-5 protein both in vitro and in vivo. Intranasal inoculation of mice with this vector or a vector expressing murine IL-6 increased adenovirus-specific im munoglobulin A (IgA) titres in lung lavage fluid threefold compared with th ose elicited by control virus. The simultaneous expression of both cytokine s by co-inoculation altered the kinetics of the mucosal anti-adenovirus IgA response and resulted in a more than additive increase in antibody titres. The co-expression effect on IgA synthesis was not due to an increase in nu mbers of antigen-specific resident lung tissue lymphocytes. When mucosal Ig G responses were examined, IL-6 expression had the largest impact on anti-a denovirus levels, whereas co-expression produced an intermediate response. Systemic immune responses were also affected by IL-6 expression as a twofol d increase in serum IgG anti-adenovirus titres was observed after a seconda ry challenge with wild-type adenovirus. These results demonstrate a relevan t role for IL-5 and IL-6 in the development of mucosal immune responses in vivo and suggest that the incorporation of either IL-5 and/or IL-6 into rec ombinant adenovirus vectors may be a useful tool in the development of muco sal vaccines.