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Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization

Authors :
A. Darise Farris
Sherry R. Crowe
Kenneth J. Smith
Lori Garman
Joel M. Guthridge
Jennifer J. Muther
Emily McKee
Patrick C. Wilson
Carla J. Guthridge
Nai-Ying Zheng
Judith A. James
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.

Details

ISSN :
0264410X
Volume :
30
Database :
OpenAIRE
Journal :
Vaccine
Accession number :
edsair.doi.dedup.....e58afe08f50def4e145f670becde25fb