Recombinant adenovirus vectors expressing interleukin‐5 and ‐6 specifically enhance mucosal immunoglobulin A responses in the lung Journal Articles uri icon

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abstract

  • SummaryIn 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 recombinant human type 5 adenoviruses capable of expressing these cytokines upon infection. A recombinant adenovirus containing the murine IL‐5 gene within 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 immunoglobulin A (IgA) titres in lung lavage fluid threefold compared with those elicited by control virus. The simultaneous expression of both cytokines 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 numbers of antigen‐specific resident lung tissue lymphocytes. When mucosal IgG responses were examined, IL‐6 expression had the largest impact on anti‐adenovirus levels, whereas co‐expression produced an intermediate response. Systemic immune responses were also affected by IL‐6 expression as a twofold increase in serum IgG anti‐adenovirus titres was observed after a secondary challenge with wild‐type adenovirus. These results demonstrate a relevant 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 recombinant adenovirus vectors may be a useful tool in the development of mucosal vaccines.

publication date

  • November 2000