{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:01:00Z","timestamp":1791036060919,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have shown that intranasal coapplication of Bacillus anthracis protective Ag (PA) together with a B. anthracis edema factor (EF) mutant having reduced adenylate cyclase activity (i.e., EF-S414N) enhances anti-PA Ab responses, but also acts as a mucosal adjuvant for coadministered unrelated Ags. To elucidate the role of edema toxin (EdTx) components in its adjuvanticity, we examined how a PA mutant lacking the ability to bind EF (PA-U7) or another mutant that allows the cellular uptake of EF, but fails to efficiently mediate its translocation into the cytosol (PA-dFF), would affect EdTx-induced adaptive immunity. Native EdTx promotes costimulatory molecule expression by macrophages and B lymphocytes, and a broad spectrum of cytokine responses by cervical lymph node cells in vitro. These effects were reduced or abrogated when cells were treated with EF plus PA-dFF, or PA-U7 instead of PA. We also intranasally immunized groups of mice with a recombinant fusion protein of Yersinia pestis F1 and LcrV Ags (F1-V) together with EdTx variants consisting of wild-type or mutants PA and EF. Analysis of serum and mucosal Ab responses against F1-V or EdTx components (i.e., PA and EF) revealed no adjuvant activity in mice that received PA-U7 instead of PA. In contrast, coimmunization with PA-dFF enhanced serum Ab responses. Finally, immunization with native PA and an EF mutant lacking adenylate cyclase activity (EF-K346R) failed to enhance Ab responses. In summary, a fully functional PA and a minimum of adenylate cyclase activity are needed for EdTx to act as a mucosal adjuvant.<\/jats:p>","DOI":"10.4049\/jimmunol.0902795","type":"journal-article","created":{"date-parts":[[2010,10,16]],"date-time":"2010-10-16T04:00:00Z","timestamp":1287201600000},"page":"5943-5952","source":"Crossref","is-referenced-by-count":21,"title":["Contributions of Edema Factor and Protective Antigen to the Induction of Protective Immunity by <i>Bacillus anthracis<\/i> Edema Toxin as an Intranasal Adjuvant"],"prefix":"10.1093","volume":"185","author":[{"given":"Alexandra","family":"Duverger","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne-Marie","family":"Carr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Ohio State University , Columbus, OH 43210"},{"name":"Laboratoire du Comportement Alimentaire, AgroParisTech , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbae","family":"Jee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H","family":"Leppla","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Cormet-Boyaka","sequence":"additional","affiliation":[{"name":"Internal Medicine, Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Jen","family":"Tang","sequence":"additional","affiliation":[{"name":"Ben Institute for Cancer Research, University of Chicago , Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Tom\u00e9","sequence":"additional","affiliation":[{"name":"Laboratoire du Comportement Alimentaire, AgroParisTech , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prosper N","family":"Boyaka","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Ohio State University , Columbus, OH 43210"},{"name":"Internal Medicine, Ohio State University , Columbus, OH 43210"},{"name":"Center for Microbial Interface Biology, Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"2025032412090648800_r1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.biochem.75.103004.142728","article-title":"Anthrax toxin: receptor binding, internalization, pore formation, and translocation","volume":"76","author":"Young","year":"2007","journal-title":"Annu. 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