Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated |
| |
| Institution: | 1. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), 825 NE 13th St., Oklahoma City, OK 73104, USA;2. Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA;3. Public Health England, National Infection Service, Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom;4. Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20814, USA;5. Department of Pharmaceutical Chemistry, University of Kansas, 320B Multidisciplinary Research Building, 2030 Becker Dr., Lawrence, KS 66047, USA;6. Departments of Medicine and Pathology, OUHSC, 1000 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA;1. Space Science Division, Naval Research Laboratory, Washington DC, USA;2. Remote Sensing Division, Naval Research Laboratory, Washington DC, USA;3. Laboratory for Atmospheric and Space Physics and Department of Atmospheric and Oceanic Sciences, University of Colorado, Boulder, CO, USA;4. GATS Inc., Driggs ID, USA;5. Computational Physics Inc., USA;6. Bradley Department of Electrical and Computer Engineering, Center for Space Science and Engineering, Virginia Tech, Blacksburg, VA, USA;7. Center for Atmsopheric Sciences, Hampton Univ, Hampton, VA, USA;1. Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, QC, Canada;2. MUHC Vaccine Study Centre – Research Institute, McGill University Health Centre, Montreal, QC, Canada;3. Direction des risques biologiques et de la santé au travail, Institut national de santé publique du Québec, Quebec City, QC, Canada;4. Department of Microbiology, Infectious Diseases and Immunology, University of Montreal, Montreal, QC, Canada;1. Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts;2. Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts;1. Medical Research Service, Veterans Affairs Medical Center, Buffalo, NY, USA;2. Departments of Ophthalmology (Ross Eye Institute) and Pathology & Anatomic Sciences, the State University of New York, Buffalo, NY, USA;3. SUNY Eye Institute, State University of New York, NY, USA;4. Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA;5. Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY, USA;6. Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA |
| |
| 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. |
| |
| Keywords: | Anthrax Anthrax vaccine adsorbed Anthrax vaccine precipitated Lethal factor Protective antigen Lethal toxin Neutralization |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
