Binding of the von Willebrand Factor A Domain of Capillary Morphogenesis Protein 2 to Anthrax Protective Antigen Vaccine Reduces Immunogenicity in Mice

Author:

de Oliveira Fabiana Freire Mendes1,Mamillapalli Sireesha2,Gonti Srinivas2,Brey Robert N.3,Li Han4,Schiffer Jarad4,Casadevall Arturo1ORCID,Bann James G.2

Affiliation:

1. Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

2. Department of Chemistry, Wichita State University, Wichita, Kansas, USA

3. Kinesis Vaccines LLC, Grayslake, Illinois, USA

4. Division of Bacterial Disease, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Abstract

The anthrax toxin PA is the major immunogen in the current anthrax vaccine (anthrax vaccine adsorbed). Improving the anthrax vaccine for avoidance of a cold chain necessitates improvements in the thermodynamic stability of PA. We address how stabilizing PA using sCMG2 affects PA immunogenicity in BALB/c mice. Although the stability of PA is increased by binding to sCMG2, PA immunogenicity is decreased. This study emphasizes that, while binding of a ligand retains or improves conformational stability without affecting the native sequence, epitope recognition or processing may be affected, abrogating an effective immune response.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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