Recombinant adenovirus vectors expressing interleukin-5 and -6 specifically enhance 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 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.
Braciak
T A
TA
Departments of Pathology and Molecular Medicine and Biology, Centre for Gene Therapeutics, McMaster University, Hamilton, Ont., Hamilton Health Sciences Corporation, Hamilton, Ont., Canada.
Gallichan
W S
WS
Graham
F L
FL
Richards
C D
CD
Ramsay
A J
AJ
Rosenthal
K L
KL
Gauldie
J
J
D000260:Adenoviruses, Human / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014765:Viral Vaccines / Q000276:immunology*
D007071:Immunoglobulin A, Secretory; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins; D014765:Viral Vaccines