Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated

Eric K. Dumas, Lori Garman, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J.M. Engler, Shyamal Choudhari, William D. Picking, Judith A. James, A. Darise Farris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective. In this report we compared humoral immune responses in cohorts of AVP (n = 39) and AVA recipients (n = 78) matched 1:2 for number of vaccinations and time post-vaccination, and evaluated whether the LF response contributes to LT neutralization in human recipients of AVP. PA response rates (≥95%) and PA IgG concentrations were similar in both groups; however, AVP recipients exhibited higher LT neutralization ED50 values (AVP: 1464.0 ± 214.7, AVA: 544.9 ± 83.2, p < 0.0001) and had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees (1%). Multiple regression analysis revealed that LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group. Affinity purified LF antibodies from two independent AVP recipients neutralized LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT neutralization. This study documents the benefit of including an LF component to PA-based anthrax vaccines.

Original languageEnglish
Pages (from-to)3416-3422
Number of pages7
JournalVaccine
Volume35
Issue number26
DOIs
Publication statusPublished - 8 Jun 2017

Bibliographical note

Funding Information:
The authors are grateful to the Walter Reed National Military Medical Center Immunization Healthcare Branch Vaccine Safety and Evaluation Section (formerly Walter Reed Army Medical Center Vaccine Healthcare Centers Network/Allergy-Immunology Research Team), the Fort Bragg Immunization Healthcare Branch Regional Vaccine Safety Hub Research Team, all of the study participants, J. Donald Capra for scientific input, Timothy Gross for assistance with affinity columns, Hua Chen for statistical analysis, Wendy Picking for overseeing production of LF fragments, Krista Bean for subject matching, as well as Rebecca Sparks, Philip Cox, Zijian Pan, Lance Pate, Clayton Nelson, Linda Ash, Aaron Guthridge, Thanh Nguyen, Wendy Klein, and Timothy Gross for technical assistance. The authors also thank Rachel Smith for production of figures and Louise Williamson for clerical assistance. This work was supported by the National Institutes of Health (NIH) [grant numbers 2U19 AI062629, P30 GM103510, U54 GM104938 and T32 AI007633] and by the OMRF J. Donald and Patricia Capra Fellowship and the OMRF Lou C. Kerr Chair in Biomedical Research. The opinions and assertions contained herein are private views of the authors and are not to be construed as official or as reflecting the views of Public Health England, the Department of Defense, Department of the Army, NIH, or other government agencies.

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • Anthrax
  • Anthrax vaccine adsorbed
  • Anthrax vaccine precipitated
  • Bacillus anthracis
  • Lethal factor
  • Lethal toxin
  • Neutralization
  • Protective antigen

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