{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:45:45Z","timestamp":1786769145849,"version":"build-2736575974"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The anthrax protective antigen (PA) is the central component of the three-part anthrax toxin, and it is the primary immunogenic component in the approved AVA anthrax vaccine and the \u201cnext-generation\u201d recombinant PA (rPA) anthrax vaccines. Animal models have indicated that PA-specific antibodies (AB) are sufficient to protect against infection with<jats:named-content content-type=\"genus-species\">Bacillus anthracis<\/jats:named-content>. In this study, we investigated the PA domain specificity, affinity, mechanisms of neutralization, and synergistic effects of PA-specific antibodies from a single donor following vaccination with the rPA vaccine. Antibody-secreting cells were isolated 7 days after the donor received a boost vaccination, and 34 fully human monoclonal antibodies (hMAb) were identified. Clones 8H6, 4A3, and 22F1 were able to neutralize lethal toxin (LeTx) both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Clone 8H6 neutralized LeTx by preventing furin cleavage of PA in a dose-dependent manner. Clone 4A3 enhanced degradation of nicked PA, thereby interfering with PA oligomerization. The mechanism of 22F1 is still unclear. A fourth clone, 2A6, that was protective only<jats:italic>in vitro<\/jats:italic>was found to be neutralizing<jats:italic>in vivo<\/jats:italic>in combination with a toxin-enhancing antibody, 8A7, which binds to domain 3 of PA and PA oligomers. These results provide novel insights into the antibody response elicited by the rPA vaccine and may be useful for PA-based vaccine and immunotherapeutic cocktail design.<\/jats:p>","DOI":"10.1128\/cvi.00792-14","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T02:33:43Z","timestamp":1426732423000},"page":"553-560","source":"Crossref","is-referenced-by-count":14,"title":["Generation and Characterization of Human Monoclonal Antibodies Targeting Anthrax Protective Antigen following Vaccination with a Recombinant Protective Antigen 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