Biomarkers of Vaccine Safety and Efficacy for Diphtheria Vaccines

Principal Investigator: Michael P. Schmitt, PhD
Office / Division / Lab: OVRR / DBPAP / LRSP

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Overview

Public Health Issue: Vaccines have been effective in the control of bacterial diseases such as diphtheria, a severe respiratory disease caused by Corynebacterium diphtheriae. However, the recent diphtheria epidemic in Russia as well as studies showing reduced immunity against diphtheria among adults in the United States and countries throughout the world has been disconcerting. These and other recent findings support a need for a new generation of vaccines that will confer longer lasting immunity, limit transmission by eradicating the organism from vaccinated people, and reduce adverse events associated with diphtheria vaccination.

Regulatory Contribution: Identifying better biomarkers of C. diphtheriae vaccine efficacy and safety will facilitate the development of new vaccines and therapeutics against diphtheria.

Research Approach: The primary aim of this research is to identify and characterize new biomarkers of virulence and attenuation factors in C. diphtheriae. Specific studies have analyzed surface proteins that are involved in the binding and acquisition of iron, an element that is thought to be essential for this bacterium to productively infect humans. Protein receptors on the surface of C. diphtheriae are candidates for a new generation of diphtheria vaccines.

Mission Relevance and Outcomes: The ultimate goal of this research is to support the development of a better-defined vaccine that will provide more effective and longer lasting immunity against diphtheria.

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Publications

J Bacteriol 2007 May;189(9):3650-4
Comparative Analysis of hmuO Function and Expression in Corynebacterium Species.
Kunkle CA, Schmitt MP

Infect Immun 2007 May;75(5):2421-31
The ChrA-ChrS and HrrA-HrrS Signal Transduction Systems are Required for Activation of the hmuO Promoter and Repression of the hemA Promoter in Corynebacterium diphtheriae.
Bibb LA, Kunkle CA, Schmitt MP

Infect Immun 2005 Nov;73(11):7406-12
Analysis of a Heme-Dependent Signal Transduction System in Corynebacterium diphtheriae: Deletion of the chrAS Genes Results in Heme Sensitivity and Diminished Heme-Dependent Activation of the hmuO Promoter.
Bibb LA, King ND, Kunkle CA, Schmitt MP

J Bacteriol 2005 Jan;187(2):422-33
Analysis of a DtxR-Regulated Iron Transport and Siderophore Biosynthesis Gene Cluster in Corynebacterium diphtheriae.
Kunkle CA, Schmitt MP

J Bacteriol 2004 Jul;186(13):4142-51
HutZ is required for efficient heme utilization in Vibrio cholerae.
Wyckoff EE, Schmitt M, Wilks A, Payne SM