Influence of the antigen delivery system on immunoglobulin isotype selection and cytokine production in response to influenza A nucleoprotein.

The influence of different antigen delivery systems on antibody isotype and lymphokine profile has been investigated using influenza nucleoprotein as a model antigen system. Mice exposed to live or inactivated influenza virus produced antibody against whole virus or recombinant nucleoprotein (rNP), which was predominantly of the IgG2a isotype. Spleen or lymph node cells from these mice rapidly produced large amounts of interferon-gamma (IFN-gamma), but no detectable interleukin-5 (IL-5) when stimulated in vitro with specific antigen. In contrast, after primary immunization with rNP or p206-229 in different adjuvants (CFA, quil A or alhydrogel), specific antibody was predominantly of the IgG1 isotype and relatively lower amounts of IFN-gamma but no IL-5 were detected following in vitro antigenic stimulation. Secondary immunization, however, resulted in detection of IgG2a antibodies and increased levels of IFN-gamma. IL-5 was only detected after secondary immunization with peptide in adjuvant. Mice infected with aro A- Salmonella typhimurium expressing NP produced antibody of both IgG1 and IgG2a isotypes and large amounts of IFN-gamma and no IL-5, following in vitro antigenic stimulation, and therefore parallelled the pattern seen with whole virus more closely than that seen following primary immunization with protein or peptide in conventional adjuvants. The results suggest that the antigen delivery vehicle influences both quantitative and qualitative differences in the type of immune response elicited, which may be important in determining the potency of protective immunity induced.