Mechanisms of Adjuvant Stimulation

Connell, Terry D.

Abstract

The goals of this project are to study the immunomodulatory activities of LT-IIa and LT-IIb. Both toxins are potent mucosal adjuvants which elicit patterns of immune responses distinct from those elicited by cholera toxin. The toxins will be used as molecular tools to investigate the mechanisms that regulate adjuvant activity. We will engineer a new class of recombinant toxins to evaluate as potential mucosal vaccines.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Research Scientist Development Award - Research (K02)
• Project #: 5K02DE014357-04
• Application #: 6839408
• Study Section: NIDCR Special Grants Review Committee (DSR)
• Program Officer: Hardwick, Kevin S
• Project Start: 2002-05-01
• Project End: 2007-01-31
• Budget Start: 2005-02-01
• Budget End: 2006-01-31
• Support Year: 4
• Fiscal Year: 2005
• Total Cost: $105,224

Institution

• Name: State University of New York at Buffalo
• Department: Microbiology/Immun/Virology
• Type: Schools of Medicine
• DUNS #: 038633251
• City: Buffalo
• State: NY
• Country: United States
• Zip Code: 14260

Publications

Lee, Chang Hoon; Nawar, Hesham F; Mandell, Lorrie et al. (2010) Enhanced antigen uptake by dendritic cells induced by the B pentamer of the type II heat-labile enterotoxin LT-IIa requires engagement of TLR2. Vaccine 28:3696-705

Nawar, Hesham F; Berenson, Charles S; Hajishengallis, George et al. (2010) Binding to gangliosides containing N-acetylneuraminic acid is sufficient to mediate the immunomodulatory properties of the nontoxic mucosal adjuvant LT-IIb(T13I). Clin Vaccine Immunol 17:969-78

Nawar, Hesham F; King-Lyons, Natalie D; Hu, John C et al. (2010) LT-IIc, a new member of the type II heat-labile enterotoxin family encoded by an Escherichia coli strain obtained from a nonmammalian host. Infect Immun 78:4705-13

Nawar, Hesham F; Arce, Sergio; Russell, Michael W et al. (2007) Mutants of type II heat-labile enterotoxin LT-IIa with altered ganglioside-binding activities and diminished toxicity are potent mucosal adjuvants. Infect Immun 75:621-33

Connell, Terry D (2007) Cholera toxin, LT-I, LT-IIa and LT-IIb: the critical role of ganglioside binding in immunomodulation by type I and type II heat-labile enterotoxins. Expert Rev Vaccines 6:821-34

Arce, Sergio; Nawar, Hesham F; Russell, Michael W et al. (2005) Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells. Infect Immun 73:2718-27