Alterations in immunodominance of the Streptococcus mutans P1 adhesin: lessons learned from immunomodulatory monoclonal antibodies (38.4)

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (1_Supplement), p.38-38.4
• Main Authors: Robinette, Rebekah, Oli, Monika, Brady, L. Jeannine, McArthur, William
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.38.4

S. mutans is the bacterial agent of human dental caries. P1 (aka AgI/II, PAc) is a surface localized multifunctional protein adhesin that has been studied as an anti-caries vaccine antigen. Our laboratory has identified several anti-P1 MAbs that redirect the host immune response via an Fc-independent mechanism toward one of improved inhibition of bacterial adherence when administered as part of an immune complex (IC) with bacterial cells in BALB/c mice. A common feature of our immunomodulatory MAbs is a requirement for certain intramolecular interactions between discontinuous segments of P1 for their epitope formation. Binding of P1 by these MAbs appears to cause a structural alteration of the cell surface adhesin exposing normally cryptic and protective epitopes. We now utilize information gained by evaluating changes in serum Abs after immunization with IC to design and evaluate structural variants of the P1 protein itself as more effective immunogens. Also, an anti-AgI/II MAb previously reported as a passive immunotherapy in clinical trials was evaluated and shown to be immunomodulatory. Results varied with MAb concentration, thus providing an explanation of long-term protection observed in human subjects and the difficulty in reproducing these results in all studies. Our results indicate a delicate balance exists between P1 structure and the availability of putative T helper cell epitopes, but suggests development of a protein-based vaccine is achievable. (NIH DE13882)