Projects & Funding

Development of Novel Adjuvants LTA and LTA1

NIH, R01AI114697, 8/2015 – 1/2020

Principal Investigator

The objective of this proposal is to develop next generation adjuvants based on the A-subunit of the heat-labile enterotoxin from Escherichia coli (LT), including LTA and LTA1. The enterotoxin family of adjuvants are powerful mucosal adjuvants, but have been hindered by major safety concerns in past clinical trials, particularly for intranasal delivery. Our preliminary studies indicate LTA and LTA1 proteins are safe and effective mucosal adjuvants because they can achieve broad mucosal and systemic immunity without the potential safety risks of the parent proteins and high levels of immunogenicity (i.e., anti-LT antibodies).


E112K as a Novel Therapy for Inflammatory Bowel Disease

BMRP, 355407, 12/2015 – 3/2018 (no cost extension)

Principal Investigator

We have discovered novel anti-inflammatory properties in a mutated bacterially-derived protein called E112K. The objective of this proposal is to determine if E112K will be beneficial in mouse models of inflammatory bowel disease (IBD), as a new therapy or prophylaxes.


Detailed LT Antibody Analysis on ETEC Clinical Trial Samples

PATH, 06/2014 – 1/2021

Principal Investigator

The goal of this project is to perform additional immunologic evaluations on serum specimens collected from an ETEC Phase 1 and 2 clinical trial for LT toxin neutralizing, conformational, and subunit-specific antibody response to enable rational vaccine design for future clinical trials.


Development of the Novel Adjuvant LT(R192G/L211A) – dmLT

BAA-NIAID-DAIT-NIH2012146: Adjuvant Development Program, 09/2013 – 09/2018

Co-Investigator (PI- J.D. Clements)

The objective of this proposal is to support the development of the novel adjuvant LT(R192G/L211A), or dmLT, toward licensure for human use with potential vaccines against two infectious diseases with significant global health implications, tuberculosis and shigellosis.


The Role of STa in ETEC Pathogenesis

NIH R01, 8/17-7/21

Co-Investigator (PI- J.P. Bitoun)

The objective of this project seeks to understand the role of heat-stable enterotoxin, ST, in ETEC pathogenesis.  Our preliminary data indicates that ST suppresses mucosal immune responses to heat-killed ETEC through manipulation of B cell class switching in GALT.  In addition, our data shows that ST binds iron and may link ETEC pathogenesis to nutritional immunity in intestinal tract.


Past Projects

Vaccine efficacy in diabetic and elderly patients

Louisiana Clinical and Translational Science Center Round 3 Pilot Grants, 6/2015 – 12/2016

Principal Investigator

Our goal is to determine if an individual’s level of inflammation determines their response to vaccination. Old age and diseases, like type-2 diabetes, are characterized as chronic inflammatory conditions and are associated with higher rates of influenza disease and health care costs. While yearly vaccination is recommended, there is a paucity of information comparing vaccination in these high-risk groups and identifying biomarkers that can predict vaccine efficacy. In this pilot proposal, we will examine adult and elderly diabetic and nondiabetic adults for markers of inflammation and vaccine efficacy before and after influenza vaccination.

Supported in part by 1 U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Physiologic and immunologic consequences of exposure to ETEC enterotoxins

NIH, R21, 8/2014 – 7/2016

Co-Investigator (PI- J.D. Clements)

Enterotoxigenic E. coli (ETEC) are a significant cause of morbidity and mortality world-wide, especially in children in developing countries. ETEC cause disease by colonizing the small intestine and producing a heat-labile (LT) and/or heat-stable (ST) enterotoxin. Despite a large fraction of LT/ST dual producing organisms, little is known about consequences of LT and ST interaction. The purpose of this study it to determine the role of LT/ST on accumulation of cyclic nucleotides in T84 cells, innate immune responses in the murine intestine, and adaptive immune responses to ETEC.


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