Back to Search
Start Over
Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization
- Source :
- Vaccine. 30:4276-4283
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- In order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (AVA), we isolated antibody secreting cells from a single donor seven days after booster vaccination with AVA and generated nine fully human monoclonal antibodies (hmAb) with high specificity for protective antigen (PA). Two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (IC(50): p6C01, 0.12 μg/ml and p6F01, 0.45 μg/ml). Passive transfer of either of these hmAbs to A/J mice prior to challenge with lethal toxin conferred 80-90% protection. We demonstrate that hmAb p6C01 is neutralizing by preventing furin cleavage of PA in a dose-dependent manner, but the mechanism of p6F01 is unclear. Three additional antibodies were found to bind to domain 3 of PA and prevent oligomerization, although they did not confer significant protection in vivo and showed a significant prozone-like effect in vitro. These fully human antibodies provide insight into the neutralizing response to AVA for future subunit vaccine and passive immunotherapeutic cocktail design.
- Subjects :
- Male
Mice, Inbred A
medicine.drug_class
Bacterial Toxins
Anthrax Vaccines
Monoclonal antibody
Article
Neutralization
Anthrax
Inhibitory Concentration 50
Mice
Antigen
Neutralization Tests
medicine
Animals
Humans
Furin
Antigens, Bacterial
Anthrax vaccines
General Veterinary
General Immunology and Microbiology
biology
Immunization, Passive
Public Health, Environmental and Occupational Health
Antibodies, Monoclonal
Anthrax Vaccine Adsorbed
Middle Aged
Antibodies, Bacterial
Antibodies, Neutralizing
Virology
Vaccination
Infectious Diseases
Proteolysis
biology.protein
Molecular Medicine
Female
Antitoxins
Protein Multimerization
Antibody
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....e58afe08f50def4e145f670becde25fb