Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHC

The generation of strong serological responses to protein antigens in experimental animals usually requires the use of potent adjuvants, most of which cannot be used in human or veterinary vaccines because of deleterious side effects. Attempting to circumvent this problem, we have assessed an adjuvant-free antigen-delivery system based on the hypothesis that antigen coupled to monoclonal antibodies (mAbs) specific for class II major histocompatibility complex (MHC) determinants should be 'targeted' onto antigen-presenting cells, thus facilitating recognition by helper T cells. We found that the biotin-binding protein avidin could generate a serological response in mice, without adjuvant, when injected coupled to a biotinylated anti-class II MHC mAb. Equivalent amounts of avidin mixed with the non-biotinylated form of the same mAb failed to elicit a response. A targeting effect was demonstrated at low levels of injected conjugate because only mice bearing the appropriate class II antigens responded. Responses were also seen with a protein antigen other than avidin, offering a new, adjuvant-free approach to subunit vaccine construction.