Bacterial Vaccine Safety: Biomarkers of Virulence and Attenuation in Bordetella Pertussis (Whooping Cough) and Anthrax Bacteria

Principal Investigator: E. Scott Stibitz, PhD
Office / Division / Lab: OVRR / DBPAP / LESTD

---

Overview

Public Health Issue: Pertussis (Whooping Cough) cases have been increasing steadily since 1975 despite widespread use of FDA licensed vaccines, with these cases occurring in regional outbreaks with regularity. Anthrax, on the other hand, represents a threat as an offensive military or terrorist weapon. In order to ensure adequate FDA preparedness for current (Pertussis) and potential (Anthrax) bacterial threats to public health, the development of scientific tools to further safe and effective vaccine development is vital.

Regulatory Contribution: This research program focuses on the development and evaluation of safer and more effective vaccines through acquisition of the scientific knowledge and tools to more efficiently evaluate bacterial vaccines.

Research Approach: This research program identifies biomarkers of virulence and attenuation of Bordetella pertussis, e.g., bvgAS mediated regulation of virulence genes, using a genetic and biochemical approach. In addition, we are developing and evaluating preclinical safety and efficacy tests, e.g., animal models of disease. The program also develops and evaluates new, more powerful, methods for using gene replacement in Bacillus anthracis and application of these methods to improve Anthrax vaccine development and to discovery of new virulence genes of Bacillus anthracis.

Mission Relevance & Outcomes: This research will provide the scientific knowledge and tools to effectively evaluate and support the development of improved Pertussis and Anthrax vaccines.

---

Publications

Infect Immun 2009 Jan;77(1):255-65
Role of anthrax toxins in dissemination, disease progression, and induction of protective adaptive immunity in the mouse aerosol challenge model.
Loving CL, Khurana T, Osorio M, Lee GM, Kelly VK, Stibitz S, Merkel TJ

Infect Immun 2009 Jan;77(1):274-85
Four superoxide dismutases contribute to Bacillus anthracis virulence and provide spores with redundant protection from oxidative stress.
Cybulski RJ Jr, Sanz P, Alem F, Stibitz S, Bull RL, O'Brien AD

Clin Vaccine Immunol 2008 Nov;15(11):1737-41
Role of the N-terminal amino acid of Bacillus anthracis lethal factor in lethal toxin cytotoxicity and its effect on the lethal toxin neutralization assay.
Verma A, Wagner L, Stibitz S, Nguyen N, Guerengomba F, Burns DL

Infect Immun 2008 Apr;76(4):1774-80
O antigen Protects Bordetella parapertussis from Complement.
Goebel EM, Wolfe DN, Elder K, Stibitz S, Harvill ET

Curr Opin Microbiol 2007 Feb;10(1):17-23
c-di-GMP-mediated regulation of virulence and biofilm formation.
Cotter PA, Stibitz S

Infect Immun 2006 Mar;74(3):1949-53
Routine markerless gene replacement in Bacillus anthracis.
Janes BK, Stibitz S

Mol Microbiol 2005 Nov;58(3):700-13
Role of BvgA phosphorylation and DNA binding affinity in control of Bvg-mediated phenotypic phase transition in Bordetella pertussis.
Jones AM, Boucher PE, Williams CL, Stibitz S, Cotter PA

Mol Microbiol 2005 Apr;56(1):175-88
BvgA functions as both an activator and a repressor to control Bvg phase expression of bipA in Bordetella pertussis.
Williams CL, Boucher PE, Stibitz S, Cotter PA

Mol Microbiol 2005 Feb;55(3):788-798
Demonstration of differential virulence gene promoter activation in vivo in Bordetella pertussis using RIVET.
Veal-Carr WL, Stibitz S