Mucosal surfaces constitute the largest and most important interface between the body and the outside environment. In addition to maintaining normal physiology, the mucosa must prevent entry, infection, and dissemination of dangerous pathogens. The innate and adaptive immune responses play pivotal roles in preventing or limiting infections. An effective vaccine can enhance this mucosal immunity without the risks and sequelae associated with primary infection.
Vaccine adjuvants can facilitate the induction and/or enhancement of protective mucosal immunity to co-administered or co-delivered antigens through their capacity to act as an immunostimulant. Some of the most potent mucosal adjuvants are the bacterially derived ADP-ribosylating enterotoxins including heat-labile toxin from Escherichia coli (LT), its mutants or subunits. This enterotoxin promotes induction of antigen-specific sIgA antibodies and long lasting memory to co-administered antigens when administered mucosally.
My research focus is mucosal immunity and immunologic mechanisms of vaccination. In particular, I am interested in how infection or vaccination can target specific cell populations involved in antigen transport and processing, enhance Th17 cell development and induce IgA production. Two particular areas of interest are mucosal administration and vaccine adjuvants, either of which can optimize protective immune responses at key mucosal surfaces.
- Mucosal immunity
- Immunologic mechanisms of vaccination
- Enhancement of protective immunity with vaccine adjuvants
Norton, E. B., Branco, L.M. Clements, J.D. Evaluating the A-subunit of the heat-labile toxin (LT) as an immunogen and a protective antigen against enterotoxigenic Escherichia coli (ETEC). PLoS One. 2015 Aug 25;10(8):e0136302. doi: 10.1371/journal.pone.0136302. eCollection 2015. PMID: 26305793
Norton E. B., Bauer D.L., Weldon W.C., Oberste M.S., Lawson L.B., Clements J.D. The novel adjuvant dmLT promotes dose sparing, mucosal immunity and longevity of antibody responses to the inactivated polio vaccine in a murine model. Vaccine. 2015;33(16):1909-15. doi: 10.1016/j.vaccine.2015.02.069. PubMed PMID: 25765967.
Read, L.T., Hahn, R.W., Thompson, C.C., Bauer, D.L., Norton, E.B., Clements, J.D. Simultaneous exposure to Escherichia coli heat-labile and heat-stable enterotoxins increases fluid secretion and alters cyclic nucleotide and cytokine production by intestinal epithelial cells. Infect Immun. 2014; 82(12):5308-16. PMID: 25483682
White, J.A., Blum, J.S., Hosken, N.A., Marshak, J.O., Duncan, L., Zhu, C., Norton, E.B., Clements, J.D., Koelle D.M., Chen, D., Lal, M. Serum and mucosal antibody responses to inactivated polio vaccine after sublingual immunization using a thermoresponsive gel delivery system. Hum Vaccin Immunother. 2014 Nov:10(12). PMID: 25483682.
Tomchuck, S.L., Norton, E.B., Garry, R.F., Bunnell, B.A., Morris, C.A., Freytag, L.C., Clements, J.D. Mesenchymal Stem Cells as a Novel Vaccine Platform. Front Cell Infect Microbiol. 2012 Nov 2: 140. PMID: 23162801.