Antigen-specific cytokine and antibody isotype profiles induced by mucosal and systemic immunization with recombinant adenoviruses.

Abstract

We investigated antigen-specific antibody and T-cell responses in mice immunized with human adenovirus type 5 (HAd5) vectors expressing either the authentic or truncated form of glycoprotein D (gD and tgD, respectively) of bovine herpesvirus type 1 (BHV-1). We also tested whether different routes of immunization influenced the level and type of immunity. Immunization intranasally (i.n.) stimulated higher levels of gD-specific IgA in the lung and nasal washes and induced a higher frequency of gD-specific antibody secreting cells (CSs) in the lung than did immunization subcutaneously (s.c.). In addition, immunization i.n. stimulated gD-specific systemic antibody responses of a higher IgG1/IgG2a ratio and lower numbers of gD-specific interferon (IFN)-gamma SCs in the spleen than did immunization s.c. HAd5-specific responses also depended on the route of immunization and were characterized by lower IFN-gamma interleukin (IL)-4 ratios than gD-specific responses. Immunization with the tgD-expressing vector induced generally lower antibody and cytokine responses than the gD-expressing vector. Higher numbers of antigen-specific IgA SCs in the lung as measured by enzyme-linked immunospot (ELISPOT) assay correlated with higher levels of IgA in the respiratory tract as measured by enzyme-linked immunosorbent (ELISA) assay, although there was no such correlation for IgG responses of any isotype. In conclusion, the route of immunization and form of antigen had an impact on the level and type of immune responses induced by adenovirus vectors.