Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals
Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from <i>Bacillus anthracis</i> spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/6/1204 |
| _version_ | 1797531644053159936 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kenneth Smith |
| collection | DOAJ |
| description | Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from <i>Bacillus anthracis</i> 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. |
| first_indexed | 2024-03-10T10:46:38Z |
| format | Article |
| id | doaj.art-3135dac548e24f40b3494cdc367ea4fd |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T10:46:38Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-3135dac548e24f40b3494cdc367ea4fd2023-11-21T22:31:11ZengMDPI AGMicroorganisms2076-26072021-06-0196120410.3390/microorganisms9061204Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated IndividualsKenneth Smith0Lori Garman1Kathleen Norris2Jennifer Muther3Angie Duke4Renata J. M. Engler5Michael R. Nelson6Limone C. Collins7Christina Spooner8Carla Guthridge9Judith A. James10Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USADepartment of Genes and Human Disease, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USADepartment of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USADepartment of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USADepartment of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USAWalter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USAWalter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USAWalter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USAWalter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USADepartment of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USADepartment of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USAAnthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from <i>Bacillus anthracis</i> 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.https://www.mdpi.com/2076-2607/9/6/1204anthraxvaccineantibodysubclassdomaintoxin |
| spellingShingle | 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 Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals Microorganisms anthrax vaccine antibody subclass domain toxin |
| title | Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals |
| title_full | Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals |
| title_fullStr | Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals |
| title_full_unstemmed | Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals |
| title_short | Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals |
| title_sort | insufficient anthrax lethal toxin neutralization is associated with antibody subclass and domain specificity in the plasma of anthrax vaccinated individuals |
| topic | anthrax vaccine antibody subclass domain toxin |
| url | https://www.mdpi.com/2076-2607/9/6/1204 |
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