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Vaccines

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Eric K. Dumas, Timothy Gross, Jason Larabee, Lance Pate, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J. M. Engler, Limone C. Collins Jr., Christina E. Spooner, Hua Chen, Jimmy Ballard, Judith A. James, A. Darise Farris
Drusilla L. Burns, Editor
Eric K. Dumas
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
bDepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA
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Timothy Gross
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
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Jason Larabee
bDepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA
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Lance Pate
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
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Hannah Cuthbertson
cPublic Health England, National Infection Service, Porton Down, Salisbury, United Kingdom
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Sue Charlton
cPublic Health England, National Infection Service, Porton Down, Salisbury, United Kingdom
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Bassam Hallis
cPublic Health England, National Infection Service, Porton Down, Salisbury, United Kingdom
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Renata J. M. Engler
dWalter Reed National Military Medical Center, Bethesda, Maryland, USA
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Limone C. Collins Jr.
dWalter Reed National Military Medical Center, Bethesda, Maryland, USA
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Christina E. Spooner
dWalter Reed National Military Medical Center, Bethesda, Maryland, USA
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Hua Chen
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
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Jimmy Ballard
bDepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA
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Judith A. James
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
eDepartments of Medicine and Pathology, OUHSC, Oklahoma City, Oklahoma, USA
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A. Darise Farris
aArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA
bDepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA
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Drusilla L. Burns
Food and Drug Administration
Roles: Editor
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DOI: 10.1128/CVI.00165-17
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ABSTRACT

Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n = 33) versus anthrax vaccine adsorbed (AVA; n = 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.

FOOTNOTES

    • Received 2 June 2017.
    • Returned for modification 29 June 2017.
    • Accepted 28 August 2017.
    • Accepted manuscript posted online 6 September 2017.
  • Supplemental material for this article may be found at https://doi.org/10.1128/CVI.00165-17 .

  • Copyright © 2017 American Society for Microbiology.

All Rights Reserved .

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Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients
Eric K. Dumas, Timothy Gross, Jason Larabee, Lance Pate, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J. M. Engler, Limone C. Collins Jr., Christina E. Spooner, Hua Chen, Jimmy Ballard, Judith A. James, A. Darise Farris
Clinical and Vaccine Immunology Nov 2017, 24 (11) e00165-17; DOI: 10.1128/CVI.00165-17

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Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients
Eric K. Dumas, Timothy Gross, Jason Larabee, Lance Pate, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J. M. Engler, Limone C. Collins Jr., Christina E. Spooner, Hua Chen, Jimmy Ballard, Judith A. James, A. Darise Farris
Clinical and Vaccine Immunology Nov 2017, 24 (11) e00165-17; DOI: 10.1128/CVI.00165-17
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KEYWORDS

Anthrax
Anthrax Vaccines
Antibodies, Bacterial
Antibodies, Neutralizing
Antigens, Bacterial
Bacillus anthracis
Bacterial Toxins
Bacillus anthracis
antibody
edema toxin
vaccine

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