{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:37:44Z","timestamp":1784216264126,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T00:00:00Z","timestamp":1529884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Science and Technology Major Project of China","award":["2016ZX10004001"],"award-info":[{"award-number":["2016ZX10004001"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Adenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of Toll\u2010like receptors (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>s) participate in the adenovirus\u2010induced adaptive immune response, yet there is little information regarding the role of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 in AdV\u2010induced immune responses in recent literature. We investigated the function of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 in both adaptive and innate immune responses to an AdV\u2010based anthrax vaccine. By immunizing wild\u2010type and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 knockout (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice, we revealed the requirement of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 in AdV\u2010induced innate responses. We also showed that <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 functions are required for germinal centre responses in immunized mice, as expression of the apoptosis\u2010related marker Fas was down\u2010regulated on germinal centre B cells from <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice. Likewise, decreased expression of inducible costimulator on follicular T helper cells was observed in immunized <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice. Moreover, a potent protective antigen\u2010specific humoral immune response was mimicked using an adjuvant system containing the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 agonist monophosphoryl lipid A. Overall, our findings showed that very rapid antigen\u2010specific antibody production is correlated with the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\u2010imprinted germinal centre response to AdV\u2010based vaccine. These results provide additional evidence for the use of the AdV and a <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> agonist to induce humoral responses. Our findings offer new insights into rational vaccine design.<\/jats:p>","DOI":"10.1111\/imm.12957","type":"journal-article","created":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T07:52:41Z","timestamp":1528357961000},"page":"251-262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Toll\u2010like receptor 4 signalling regulates antibody response to adenoviral vector\u2010based vaccines by imprinting germinal centre quality"],"prefix":"10.1111","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9645-5226","authenticated-orcid":false,"given":"Ruihua","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Vaccine and Antibody Engineering Beijing Institute of Biotechnology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine and Antibody Engineering Beijing Institute 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Beijing Institute of Biotechnology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Hou","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine and Antibody Engineering Beijing Institute of Biotechnology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine and Antibody Engineering Beijing Institute of Biotechnology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine and Antibody Engineering Beijing Institute of Biotechnology Beijing 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