Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals

Kenneth Smith; Lori Garman; Kathleen Norris; Jennifer Muther; Angie Duke; Renata J. M. Engler; Michael R. Nelson; Limone C. Collins; Christina Spooner; Carla Guthridge; Judith A. James

doi:10.3390/microorganisms9061204

Microorganisms (Jun 2021)

Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals

Kenneth Smith,
Lori Garman,
Kathleen Norris,
Jennifer Muther,
Angie Duke,
Renata J. M. Engler,
Michael R. Nelson,
Limone C. Collins,
Christina Spooner,
Carla Guthridge,
Judith A. James

Affiliations

Kenneth Smith: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Lori Garman: Department of Genes and Human Disease, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Kathleen Norris: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Jennifer Muther: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Angie Duke: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Renata J. M. Engler: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USA
Michael R. Nelson: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USA
Limone C. Collins: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USA
Christina Spooner: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USA
Carla Guthridge: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA
Judith A. James: Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA

DOI: https://doi.org/10.3390/microorganisms9061204
Journal volume & issue: Vol. 9, no. 6
p. 1204

Abstract

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Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from Bacillus anthracis spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin. In this cohort, characterized by poorly neutralizing antibody, we find that increased IgG4 to IgG1 subclass ratios, low antibody avidity, and insufficient antibody targeting domain 4 associate with improper neutralization. Thus, future vaccines and vaccination schedules should be formulated to improve these deficiencies.

Published in Microorganisms

ISSN: 2076-2607 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.mdpi.com/journal/microorganisms

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