Novel use of peptide triazole virucides to generate HIV-1env vaccine antigens that elicit in vivo neutralizing antibody responses to the Membrane Proximal External Region of envelope glycoprotein
The overarching goal of this project will be to use relevant animal models to characterize the in vivo immune potency and functional anti-HIV breadth of novel HIV-1env vaccine antigens purified from peptide-triazole-treated residual viral particles that contain antigenically active gp41 spikes. The aim of this study is to test the hypothesis that delivery of peptide triazole-treated HIV-1 pseudoviral particle fractions to mice and rabbits in vivo will result in the development of both anti-HIV CD4 and CD8 T-cells, as well as antibody responses that will map to specific immunoreactive relevant MPER gp41 epitopes.
Impaired immune priming and diminished B cell repertoires in aging models of CDIFF
There is a significant correlation between advanced age and risk of severe and recurrent Clostridium difficile infection (CDI). Aged individuals have a reduced ability to produce high affinity anti-toxin antibodies, but it has yet to be determined whether the defect in the elderly is due to lack of host immune priming to CDI and/or a decrease in B cell repertoire diversity making individuals more susceptible to severe disease. The purpose of this project is to identify age related functional changes in the B cell populations in the context of Clostridium difficile infection using a novel aging mouse model of CDI developed in our laboratory.
Non-Thermal Plasma as an Effective DNA Vaccine Adjuvant
This proposal outlines studies in the field of plasma medicine, which is a rapidly expanding field of translational research that revolves around the use of electrically generated plasma for various biomedical applications. The first goal is to establish the feasibility of dielectric barrier discharge (DBD) plasma as an adjuvant during the delivery of DNA-based vaccines. These studies will progress from in vitro experiments designed to demonstrate the biological effects of DBD plasma on human epithelial and immune cells to a mouse model of DNA vaccine delivery augmented by DBD plasma application. The second related goal will be to expand our knowledge of the biological effects of DBD plasma application. My role on the project is to provide expertise in the area of DNA vaccine delivery and adjuvant systems.
CD4 T cell function in aging responses to C. diff infection and vaccination
Clostridium difficile infection (CDI) is a major source of morbidity and mortality, costs the United States healthcare system approximately $1.1 billion/year, has a 23% annual increased diagnosis rate since 2000, and leads to a doubling of mortality with greater than 90% of these deaths being attributed to individuals who are older than 85 years-old. The goal of this application is to determine the requirement of CD4 T helper cell co-stimulatory pathways in the development of host anti-toxin neutralizing antibodies in an aging cohort during CDI in order to better design molecular vaccine adjuvants that target these critical pathways resulting in protective humoral immune responses in our DNA vaccine platform in the elderly.
Mu-Opioid modulation of chemokines and HIV replication
Mu-Opioid regulation of mucosal immunity against C. diff
TNT: Use of CCL28 target and trigger mucosal immunity to EP HIV-1 DNA
CD4 T helper cell functional requirements in the aging response to C. diff
Manipulation of C. diff using an anaerobic chamber in the laboratory
Development of luciferase-expressing C. diff for use in IVIS
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