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  1. Biologics Research Projects

Improving Vaccine Manufacturing Evaluation for Bacterial Respiratory Pathogens

Principal Investigator: Drusilla L. Burns, PhD
Office / Division / Lab: OVRR / DBPAP / LRSP

General Overview

CBER is responsible for ensuring that the vaccines that are made available to the public are safe, pure, and potent. In order to do this, a solid understanding of the science of vaccines is required. Knowledge of both pathogenic mechanisms and host response is essential for proper regulation of vaccines since this knowledge allows us to identify the features of vaccine antigens that are critical to ensure safe and effective vaccines.

The research in this Laboratory Section supports the specific regulatory responsibilities of the individuals of the section which include review of pertussis, anthrax and Staphylococcal aureus vaccine regulatory submissions by providing us with knowledge about how Bordetella pertussis, Bacillus anthracis, and Staphylococcus aureus cause disease as well how the host immune response controls infection and disease.

These studies provide new scientific tools and knowledge required to support the manufacturing and clinical evaluation of pertussis, anthrax, and S. aureus vaccines. The program also develops and evaluates in-process tests and vaccine lot release tests, including stability tests, as well as clinical serological assays that measure antibody levels for evaluation of vaccines.

Scientific Overview

We use biochemical, genetic and molecular biological techniques to study pathogenesis and host response and to further characterize vaccine components, especially those for pertussis, anthrax, and S. aureus vaccines. We are also using these techniques to analyze and quantify the host immune response to infection and vaccination.

Primarily, these techniques include SDS polyacrylamide gel electrophoresis, immunoblot analysis, and recombinant DNA techniques to better understand the role of bacterial virulence factors-especially toxins and adhesins, in disease.

The program also develops and evaluates in-process tests and vaccine lot release tests, including stability tests, as well as clinical serological assays that measure antibody levels for evaluation of vaccines.


Pharmeur Bio Sci Notes 2016;2015:97-114
Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.
Isbrucker R, Daas A, Wagner L, Costanzo A

Pharmeur Bio Sci Notes 2016;2015:82-96
Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement.
Arciniega J, Wagner L, Prymula R, Sebo P, Isbrucker R, Descampe B, Chapsal JM, Costanzo A, Hendriksen C, Hoonaker M, Nelson S, Lidster K, Casey W, Allen D

Clin Vaccine Immunol 2016 May 6;23(5):396-402
Mechanistic analysis of the effect of deamidation on the immunogenicity of anthrax protective antigen.
Verma A, Ngundi MM, Burns DL

PLoS One 2015 Apr 22;10(4):e0124877
RNA-Seq analysis of the host response to Staphylococcus aureus skin and soft tissue infection in a mouse model.
Brady RA, Bruno VM, Burns DL

Clin Vaccine Immunol 2014 Apr;21(4):580-6
Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.
Feinen B, Petrovsky N, Verma A, Merkel TJ

J Infect Dis 2014 Apr;209 Suppl 1:S28-31
Clinical evaluation of pertussis vaccines: US Food and Drug Administration regulatory considerations.
Farizo KM, Burns DL, Finn TM, Gruber MF, Pratt RD

J Infect Dis 2014 Apr;209(7):982-5
Pertussis pathogenesis--what we know and what we don't know.
Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP, Stibitz ES

J Infect Dis 2014 Apr;209 Suppl 1:S32-5
Pertussis resurgence: perspectives from the Working Group Meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge.
Burns DL, Meade BD, Messionnier NE

Clin Vaccine Immunol 2014 May;21(5):622-7
Role of antibodies in protection elicited by active vaccination with genetically inactivated alpha hemolysin in a mouse model of staphylococcus aureus skin and soft tissue infections.
Mocca CP, Brady RA, Burns DL

Clin Vaccine Immunol 2013 Aug;20(8):1338-40
Immunogenicity analysis of Staphylococcus aureus clumping factor A genetic variants.
Brady RA, Mocca CP, Burns DL

PLoS One 2013 Apr 29;8(4):e63040
Evaluation of genetically inactivated alpha toxin for protection in multiple mouse models of Staphylococcus aureus infection.
Brady RA, Mocca CP, Prabhakara R, Plaut RD, Shirtliff ME, Merkel TJ, Burns DL

Infect Immun 2013 Jan;81(1):278-84
Use of site-directed mutagenesis to model the effects of spontaneous deamidation on the immunogenicity of Bacillus anthracis protective antigen.
Verma A, McNichol B, Domínguez-Castillo RI, Amador-Molina JC, Arciniega JL, Reiter K, Meade BD, Ngundi MM, Stibitz S, Burns DL

Clin Vaccine Immunol 2012 Sep;19(9):1465-73
Structural and immunological analysis of anthrax recombinant protective antigen adsorbed to aluminum hydroxide adjuvant.
Wagner L, Verma A, Meade BD, Reiter K, Narum DL, Brady RA, Little SF, Burns DL

Curr Opin Virol 2012 Jun;2(3):353-6
Licensure of vaccines using the Animal Rule.
Burns DL

Clin Vaccine Immunol 2012 May;19(5):731-9
Analysis of defined combinations of monoclonal antibodies in anthrax toxin neutralization assays and their synergistic action.
Ngundi MM, Meade BD, Little SF, Quinn CP, Corbett CR, Brady RA, Burns DL

Proc Natl Acad Sci U S A 2010 Oct 19;107(42):18091-6
Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities.
Merkel TJ, Perera PY, Kelly VK, Verma A, Llewellyn ZN, Waldmann TA, Mosca JD, Perera LP

Clin Vaccine Immunol 2010 Sep;17(9):1390-7
Analysis of antibody responses to protective antigen-based anthrax vaccines through use of competitive assays.
Brady RA, Verma A, Meade BD, Burns DL

Clin Vaccine Immunol 2010 Jun;17(6):895-903
Comparison of Three Anthrax Toxin Neutralization Assays.
Ngundi MM, Meade BD, Lin TL, Tang WJ, Burns DL

Vaccine 2010 Jun 23;28(29):4539-47
Utilization of serologic assays to support efficacy of vaccines in nonclinical and clinical trials: meeting at the crossroads.
Madore DV, Meade BD, Rubin F, Deal C, Lynn F, Meeting Contributors

Clin Vaccine Immunol 2009 Dec;16(12):1781-8
Development and Analytical Validation of Immunoassay for Quantifying Serum Anti-Pertussis Toxin Antibodies Resulting from Bordetella pertussis Infection.
Menzies SL, Kadwad V, Pawloski L, Lin TL, Baughman AL, Martin M, Tondella ML, Meade BD, the Pertussis Assay Working Group

Infect Immun 2009 Oct;77(10):4182-6
The Case for Developing Consensus Standards for Research in Microbial Pathogenesis: Bacillus anthracis Toxins as an Example.
Hughes MA, Burns DL, Juris SJ, Tang WJ, Clement KH, Eaton LJ, Kelly-Cirino CD, McKee ML, Powell BS, Bishop BL, Rudge TL, Shine N, Verma A, Willis MS, Morse SA

Vaccine 2009 Jul 16;27(33):4537-42
Comparability of ELISA and toxin neutralization to measure immunogenicity of Protective Antigen in mice, as part of a potency test for anthrax vaccines.
Parreiras PM, Sirota LA, Wagner LD, Menzies SL, Arciniega JL

J Bacteriol 2008 Nov;190(21):7285-90
Stabilization of the Pertussis Toxin Secretion Apparatus by the C-terminus of PtlD.
Verma A, Cheung AM, Burns DL

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

Clin Vaccine Immunol 2008 Jun;15(6):946-53
Interlaboratory Comparison of the Anthrax Lethal Toxin Neutralization Assay used to Assess Functional Antibodies in Multiple Species.
Omland KS, Brys A, Lansky D, Clement K, Lynn F, Participating Laboratories

Infect Immun 2007 May;75(5):2297-306
Requirements for Assembly of PtlH with the Pertussis Toxin Transporter Apparatus of Bordetella pertussis.
Verma A, Burns DL

Infect Immun 2005 Aug;73(8):5222-8
Importance of srtA and srtB for Growth of Bacillus anthracis in Macrophages.
Zink SD, Burns DL