{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:17:59Z","timestamp":1790745479698,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Francisella tularensis<\/jats:named-content>, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad\/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, of<jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>LVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 \u00d7 10<jats:sup>7<\/jats:sup>PFU) of Ad\/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 \u00d7 50% lethal dose (LD<jats:sub>50<\/jats:sub>)<jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>LVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 \u03bcg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad\/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain of<jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 of<jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>LVS.<\/jats:p>","DOI":"10.1128\/cvi.05384-11","type":"journal-article","created":{"date-parts":[[2012,1,26]],"date-time":"2012-01-26T06:13:29Z","timestamp":1327558409000},"page":"359-364","source":"Crossref","is-referenced-by-count":19,"title":["Protective Immunity against Tularemia Provided by an Adenovirus-Vectored Vaccine Expressing Tul4 of Francisella tularensis"],"prefix":"10.1128","volume":"19","author":[{"given":"Ravinder","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Ar\u00e9valo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingtao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2012,1,25]]},"reference":[{"key":"key20180919073557_B1","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1128\/JVI.72.2.1497-1503.1998","article-title":"Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage","volume":"72","author":"Andr\u00e9","year":"1998","journal-title":"J. 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