{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:12:51Z","timestamp":1760231571574,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"US National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1 DP1DA033502","R42 DA043311"],"award-info":[{"award-number":["1 DP1DA033502","R42 DA043311"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Anti-drug vaccines previously failed clinical trials because they did not provide a sufficient titer or duration of antibodies (AB), but new adjuvants enhance both AB titers and efficacy duration. This clinical trial assessed AB titers after a single booster of commercial tetanus-diphtheria (Td) vaccine in 40 males randomized as 15 to Td alone and 25 to Td combined with the TLR5 adjuvant, Entolimod (Ent). Ent significantly increased ABs against diphtheria (DPT) (0.46 vs. 0.29 IU\/mL increase; n = 40, p &lt; 0.05), but against tetanus (TT) only if baseline TT AB was below 3 IU\/mL (3.1 vs. 2.1 IU\/mL; n = 20; p &lt; 0.05). These 20 participants also showed a two-fold increase in anti-TT AB titer more often when given Ent than non-Ent (33% vs. 82%) (p &lt; 0.03). Anti-Ent AB was low and appeared unlikely to reduce Ent efficacy after repeated Ent administration. Medical safety was excellent, and a TLR5 missense polymorphism reduced anti-DPT AB production, but Ent increased anti-DPT AB titers to levels induced in subjects with genetically \u201cnormal\u201d TRL5 functioning. Further clinical testing of TLR5 adjuvants like Ent seems warranted for anti-drug vaccines.<\/jats:p>","DOI":"10.3390\/vaccines10101592","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T04:07:07Z","timestamp":1663906027000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Clinical Trial of Entolimod a TLR-5 Adjuvant for Vaccines Using Diphtheria or Tetanus as Carrier Proteins"],"prefix":"10.3390","volume":"10","author":[{"given":"Thomas R.","family":"Kosten","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Immunology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coreen B.","family":"Domingo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Immunology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-7291","authenticated-orcid":false,"given":"Colin N.","family":"Haile","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Houston, Houston, TX 77004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1080\/14760584.2017.1378577","article-title":"Current status and future prospects for the development of substance abuse vaccines","volume":"16","author":"Heekin","year":"2017","journal-title":"Expert Rev. 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