Induction in mucosa of IgG and IgA antibodies against parenterally administered soluble immunogens

The induction of a mucosal immunity provides an additional principle of vaccination by preventing the entry of pathogens in the body. Albeit the fact that intensive research has been conducted on local vaccines, the major mucosal vaccine commercially available for human use remains the oral polio vaccine. We have previously demonstrated that parenteral vaccination in humans with tetanus toxoid (TT) results in a genital immunoglobulin (Ig)G antibody (Ab) response. Here, we show that injections of TT with no adjuvant induces an anti-TT response in the mucosal tissues of normal BALB/c mice. The response is multiregional, involves both IgG and IgA isotypes, and is long-lasting. Similarly, injections of haptens coupled to TT or to other diffusible proteins may induce mucosal Abs. These results led us to immunize normal BALB/c mice with a viral peptide coupled to TT by disulfide bridging. The hapten was a 17 amino acid peptide containing the ELDKWA sequence of human immunodeficiency virus (HIV)-1 gp41. A significant IgG and IgA Ab response to the immunizing peptide was induced in various mucosal tissues despite the presence of a suboptimal Ab response in the spleen. The results indicate that mucosal immunity to peptides that are candidates for human vaccinations may be achieved by parenteral adjuvant-free immunization with peptide coupled to TT.