{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:37:14Z","timestamp":1789094234171,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004919","name":"King Abdulaziz City for Science and Technology","doi-asserted-by":"publisher","award":["AT-35\u2013171"],"award-info":[{"award-number":["AT-35\u2013171"]}],"id":[{"id":"10.13039\/501100004919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Infection control measures have played a major role in limiting human\/camel-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV); however, development of effective and safe human or camel vaccines is warranted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extended and optimized our previous recombinant adenovirus 5 (rAd5)\u2013based vaccine platform characterized by in vivo amplified and CD40-mediated specific responses to generate MERS-CoV S1 subunit-based vaccine. We generated rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1\/F\/CD40L), untargeted S1 (rAd5-S1), and Green Fluorescent Protein (rAd5-GFP), and evaluated their efficacy and safety in human dipeptidyl peptidase 4 transgenic (hDPP4 Tg+) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunization of hDPP4 Tg+ mice with a single dose of rAd5-S1\/F\/CD40L elicited as robust and significant specific immunoglobulin G and neutralizing antibodies as those induced with 2 doses of rAd5-S1. After MERS-CoV challenge, both vaccines conferred complete protection against morbidity and mortality, as evidenced by significantly undetectable\/reduced pulmonary viral loads compared to the control group. However, rAd5-S1\u2013 but not rAd5-S1\/F\/CD40L\u2013immunized mice exhibited marked pulmonary perivascular hemorrhage post\u2013MERS-CoV challenge despite the observed protection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Incorporation of CD40L into rAd5-based MERS-CoV S1 vaccine targeting molecule and molecular adjuvants not only enhances immunogenicity and efficacy but also prevents inadvertent pulmonary pathology after viral challenge, thereby offering a promising strategy to enhance safety and potency of vaccines.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiz137","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T04:17:04Z","timestamp":1553228224000},"page":"1558-1567","source":"Crossref","is-referenced-by-count":69,"title":["A Highly Immunogenic, Protective, and Safe Adenovirus-Based Vaccine Expressing Middle East Respiratory Syndrome Coronavirus S1-CD40L Fusion Protein in a Transgenic Human Dipeptidyl Peptidase 4 Mouse Model"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-7011","authenticated-orcid":false,"given":"Anwar M","family":"Hashem","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine"},{"name":"Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, Saudi Arabia"},{"name":"Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Algaissi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston"},{"name":"Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurodh Shankar","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan S","family":"Al-amri","sequence":"additional","affiliation":[{"name":"Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, Saudi Arabia"},{"name":"Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowa Y","family":"Alhabbab","sequence":"additional","affiliation":[{"name":"Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, Saudi Arabia"},{"name":"Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed S","family":"Sohrab","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"S. Almasoud","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naif Khalaf","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Hung","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha","family":"Russell","sequence":"additional","affiliation":[{"name":"Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, 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