{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:26:43Z","timestamp":1789885603515,"version":"4.0.1"},"reference-count":132,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T00:00:00Z","timestamp":1547683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI100625"],"award-info":[{"award-number":["U19AI100625"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R00AG049092"],"award-info":[{"award-number":["R00AG049092"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007865","name":"University of Texas Medical Branch","doi-asserted-by":"publisher","award":["McLaughlin Endowment"],"award-info":[{"award-number":["McLaughlin Endowment"]}],"id":[{"id":"10.13039\/100007865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.<\/jats:p>","DOI":"10.3390\/v11010074","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T11:30:27Z","timestamp":1547724627000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism"],"prefix":"10.3390","volume":"11","author":[{"given":"Craig","family":"Schindewolf","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, 77555 TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-7606","authenticated-orcid":false,"given":"Vineet D.","family":"Menachery","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, 77555 TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14040","DOI":"10.1073\/pnas.0506735102","article-title":"Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats","volume":"102","author":"Lau","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJMp0904572","article-title":"Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus","volume":"361","author":"Trifonov","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1126\/science.1259657","article-title":"Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak","volume":"345","author":"Gire","year":"2014","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1056\/NEJMoa1404505","article-title":"Emergence of Zaire Ebola virus disease in Guinea","volume":"371","author":"Baize","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/bs.aivir.2016.08.008","article-title":"The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing","volume":"96","author":"Snijder","year":"2016","journal-title":"Adv. Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/jmv.1890060309","article-title":"Coronavirus infections of man associated with diseases other than the common cold","volume":"6","author":"Riski","year":"1980","journal-title":"J. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/CMR.00102-14","article-title":"Middle East respiratory syndrome coronavirus: Another zoonotic betacoronavirus causing SARS-like disease","volume":"28","author":"Chan","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.1118391","article-title":"Bats are natural reservoirs of SARS-like coronaviruses","volume":"310","author":"Li","year":"2005","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Anthony, S.J., Gilardi, K., Menachery, V.D., Goldstein, T., Ssebide, B., Mbabazi, R., Navarrete-Macias, I., Liang, E., Wells, H., and Hicks, A. (2017). Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus. mBio, 8.","DOI":"10.1128\/mBio.00373-17"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/nm.3985","article-title":"A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence","volume":"21","author":"Menachery","year":"2015","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S0140-6736(15)60454-8","article-title":"Middle East respiratory syndrome","volume":"386","author":"Zumla","year":"2015","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.3201\/eid2012.141026","article-title":"MERS coronavirus neutralizing antibodies in camels, Eastern Africa, 1983\u20131997","volume":"20","author":"Muller","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMoa1401505","article-title":"Evidence for camel-to-human transmission of MERS coronavirus","volume":"370","author":"Azhar","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"The Health Protection Agency (HPA) UK Novel Coronavirus Investigation Team (2013). Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013. Euro Surveill., 18, 20427.","DOI":"10.2807\/ese.18.11.20427-en"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrd.2015.37","article-title":"Coronaviruses-drug discovery and therapeutic options","volume":"15","author":"Zumla","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1128\/AAC.03036-14","article-title":"Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection","volume":"58","author":"Dyall","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","unstructured":"Public Health England\/ISARIC (2015). Treatment of MERS-CoV: Information for Clinicians, Clinical Decision-Making Support for Treatment of MERS-CoV Patients, Public Health England."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.onehlt.2017.03.001","article-title":"Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus","volume":"3","author":"Vidal","year":"2017","journal-title":"One Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature12005","article-title":"Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC","volume":"495","author":"Raj","year":"2013","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1128\/JVI.03445-14","article-title":"Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection","volume":"89","author":"Peck","year":"2015","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1128\/JVI.03764-13","article-title":"Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection","volume":"88","author":"Cockrell","year":"2014","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1099\/vir.0.060640-0","article-title":"Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus","volume":"95","author":"Coleman","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16226","DOI":"10.1038\/nmicrobiol.2016.226","article-title":"A mouse model for MERS coronavirus-induced acute respiratory distress syndrome","volume":"2","author":"Cockrell","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4970","DOI":"10.1073\/pnas.1323279111","article-title":"Rapid generation of a mouse model for Middle East respiratory syndrome","volume":"111","author":"Zhao","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8738","DOI":"10.1073\/pnas.1510830112","article-title":"Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection","volume":"112","author":"Pascal","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1128\/JVI.02009-15","article-title":"Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease","volume":"90","author":"Tao","year":"2016","journal-title":"J. Virol."},{"key":"ref_27","first-page":"E3119","article-title":"Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro2090","article-title":"The spike protein of SARS-CoV\u2014A target for vaccine and therapeutic development","volume":"7","author":"Du","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1586\/14760584.2014.912134","article-title":"Current advancements and potential strategies in the development of MERS-CoV vaccines","volume":"13","author":"Zhang","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.meegid.2007.07.004","article-title":"The SARS-CoV nucleocapsid protein: A protein with multifarious activities","volume":"8","author":"Surjit","year":"2008","journal-title":"Infect. Genet. Evolut."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.drudis.2015.11.015","article-title":"Recent insights into the development of therapeutics against coronavirus diseases by targeting N protein","volume":"21","author":"Chang","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15214","DOI":"10.1073\/pnas.1407087111","article-title":"Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein","volume":"111","author":"Millet","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E8508","DOI":"10.1073\/pnas.1712592114","article-title":"Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E7348","DOI":"10.1073\/pnas.1707304114","article-title":"Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen","volume":"114","author":"Pallesen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"234ra59","DOI":"10.1126\/scitranslmed.3008140","article-title":"Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein","volume":"6","author":"Jiang","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Irigoyen, N., Firth, A.E., Jones, J.D., Chung, B.Y., Siddell, S.G., and Brierley, I. (2016). High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005473"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9804","DOI":"10.1073\/pnas.0403492101","article-title":"Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity","volume":"101","author":"Buchholz","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/infdis\/jit609","article-title":"Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses","volume":"209","author":"Agnihothram","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.imlet.2004.01.001","article-title":"Induction of SARS-nucleoprotein-specific immune response by use of DNA vaccine","volume":"92","author":"Zhu","year":"2004","journal-title":"Immunol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s12026-014-8534-z","article-title":"T cell-mediated immune response to respiratory coronaviruses","volume":"59","author":"Channappanavar","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1128\/JVI.78.11.5612-5618.2004","article-title":"T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS","volume":"78","author":"Wang","year":"2004","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhao, J., Alshukairi, A.N., Baharoon, S.A., Ahmed, W.A., Bokhari, A.A., Nehdi, A.M., Layqah, L.A., Alghamdi, M.G., Al Gethamy, M.M., and Dada, A.M. (2017). Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses. Sci. Immunol., 2.","DOI":"10.1126\/sciimmunol.aan5393"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Deming, D., Sheahan, T., Heise, M., Yount, B., Davis, N., Sims, A., Suthar, M., Harkema, J., Whitmore, A., and Pickles, R. (2006). Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030525"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Tseng, C.T., Sbrana, E., Iwata-Yoshikawa, N., Newman, P.C., Garron, T., Atmar, R.L., Peters, C.J., and Couch, R.B. (2012). Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS ONE, 7.","DOI":"10.1371\/annotation\/2965cfae-b77d-4014-8b7b-236e01a35492"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43330","DOI":"10.1074\/jbc.M405001200","article-title":"Crystal structure of CD26\/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface","volume":"279","author":"Weihofen","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.antiviral.2016.07.015","article-title":"MERS-CoV spike protein: Targets for vaccines and therapeutics","volume":"133","author":"Wang","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1042\/BA20000034","article-title":"Design and production of recombinant subunit vaccines","volume":"32","author":"Hansson","year":"2000","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/1743-422X-7-299","article-title":"Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients","volume":"7","author":"Cao","year":"2010","journal-title":"Virol. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9939","DOI":"10.1128\/JVI.01048-13","article-title":"Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development","volume":"87","author":"Du","year":"2013","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9379","DOI":"10.1128\/JVI.01277-13","article-title":"The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies","volume":"87","author":"Mou","year":"2013","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2000.0239","article-title":"Antibody and virus: Binding and neutralization","volume":"270","author":"Burton","year":"2000","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/j.vaccine.2014.02.004","article-title":"Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines","volume":"32","author":"Ma","year":"2014","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.vaccine.2008.11.083","article-title":"Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogen","volume":"27","author":"Zhang","year":"2009","journal-title":"Vaccine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6170","DOI":"10.1016\/j.vaccine.2014.08.086","article-title":"Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments\u2014The importance of immunofocusing in subunit vaccine design","volume":"32","author":"Ma","year":"2014","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/j.vaccine.2018.02.065","article-title":"Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen","volume":"36","author":"Nyon","year":"2018","journal-title":"Vaccine"},{"key":"ref_56","first-page":"817","article-title":"The carboxy-terminal domain initiates trimerization of bacteriophage T4 fibritin","volume":"64","author":"Letarov","year":"1999","journal-title":"Biochem. Biokhimiia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.virol.2016.10.005","article-title":"A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection","volume":"499","author":"Tai","year":"2016","journal-title":"Virology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.ebiom.2015.08.031","article-title":"Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge","volume":"2","author":"Lan","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e01651-16","DOI":"10.1128\/JVI.01651-16","article-title":"Recombinant Receptor-Binding Domains of Multiple Middle East Respiratory Syndrome Coronaviruses (MERS-CoVs) Induce Cross-Neutralizing Antibodies against Divergent Human and Camel MERS-CoVs and Antibody Escape Mutants","volume":"91","author":"Tai","year":"2017","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1016\/j.vaccine.2014.04.016","article-title":"Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice","volume":"32","author":"Coleman","year":"2014","journal-title":"Vaccine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.vaccine.2017.02.012","article-title":"MERS-CoV spike nanoparticles protect mice from MERS-CoV infection","volume":"35","author":"Coleman","year":"2017","journal-title":"Vaccine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.vaccine.2006.08.011","article-title":"Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro","volume":"25","author":"Kam","year":"2007","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1126\/science.1243283","article-title":"Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus","volume":"342","author":"McLellan","year":"2013","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.1085952","article-title":"Characterization of a novel coronavirus associated with severe acute respiratory syndrome","volume":"300","author":"Rota","year":"2003","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.vaccine.2016.11.064","article-title":"The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection","volume":"35","author":"Jiaming","year":"2017","journal-title":"Vaccine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nbt0998-867","article-title":"Gene transfer into muscle by electroporation in vivo","volume":"16","author":"Aihara","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.coi.2011.03.008","article-title":"Electroporation delivery of DNA vaccines: Prospects for success","volume":"23","author":"Sardesai","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1600-065X.2010.00980.x","article-title":"DNA vaccines: An historical perspective and view to the future","volume":"239","author":"Liu","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1749-6632.1995.tb44729.x","article-title":"Potential DNA vaccine integration into host cell genome","volume":"772","author":"Nichols","year":"1995","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/toxsci\/kfj169","article-title":"Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts","volume":"91","author":"Sheets","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"301ra132","DOI":"10.1126\/scitranslmed.aac7462","article-title":"A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates","volume":"7","author":"Muthumani","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8828","DOI":"10.1128\/JVI.79.14.8828-8834.2005","article-title":"A human T-cell leukemia virus type 1 regulatory element enhances the immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and nonhuman primates","volume":"79","author":"Barouch","year":"2005","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1365-2567.2011.03525.x","article-title":"Robust immune response elicited by a novel and unique Mycobacterium tuberculosis protein using an optimized DNA\/protein heterologous prime\/boost protocol","volume":"135","author":"Cayabyab","year":"2012","journal-title":"Immunology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7712","DOI":"10.1038\/ncomms8712","article-title":"Evaluation of candidate vaccine approaches for MERS-CoV","volume":"6","author":"Wang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1016\/j.vaccine.2017.02.063","article-title":"DNA vaccine encoding Middle East respiratory syndrome coronavirus S1 protein induces protective immune responses in mice","volume":"35","author":"Chi","year":"2017","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S0952-7915(96)80124-5","article-title":"Mechanisms of antigen uptake for presentation","volume":"8","author":"Lanzavecchia","year":"1996","journal-title":"Curr. Opin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"44875","DOI":"10.1038\/srep44875","article-title":"Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein","volume":"7","author":"Abbas","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/334255a0","article-title":"Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells","volume":"334","author":"Stevens","year":"1988","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.coi.2011.03.006","article-title":"Viral vectors as vaccine platforms: Deployment in sight","volume":"23","author":"Rollier","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/viro.1997.8878","article-title":"Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: Expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo","volume":"239","author":"Pushko","year":"1997","journal-title":"Virology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e00027-18","DOI":"10.1128\/JVI.00027-18","article-title":"Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform","volume":"92","author":"Agnihothram","year":"2018","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.immuni.2016.05.006","article-title":"Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses","volume":"44","author":"Zhao","year":"2016","journal-title":"Immunity"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10847","DOI":"10.1073\/pnas.89.22.10847","article-title":"Nonreplicating vaccinia vector efficiently expresses recombinant genes","volume":"89","author":"Sutter","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1016\/S0264-410X(01)00075-5","article-title":"Safety of modified vaccinia virus Ankara (MVA) in immune-suppressed macaques","volume":"19","author":"Stittelaar","year":"2001","journal-title":"Vaccine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11950","DOI":"10.1128\/JVI.01672-13","article-title":"Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies","volume":"87","author":"Song","year":"2013","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8651","DOI":"10.1128\/JVI.00614-15","article-title":"Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein","volume":"89","author":"Volz","year":"2015","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.biologicals.2018.05.004","article-title":"Distribution and absence of generalized lesions in mice following single dose intramuscular inoculation of the vaccine candidate MVA-MERS-S","volume":"54","author":"Langenmayer","year":"2018","journal-title":"Biologicals"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.aad1283","article-title":"An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels","volume":"351","author":"Haagmans","year":"2016","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1056\/NEJMoa1310566","article-title":"Efficacy trial of a DNA\/rAd5 HIV-1 preventive vaccine","volume":"369","author":"Hammer","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/sj.gt.3300994","article-title":"Immune responses to adenovirus and adeno-associated virus in humans","volume":"6","author":"Chirmule","year":"1999","journal-title":"Gene Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.vaccine.2009.10.145","article-title":"International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials","volume":"28","author":"Mast","year":"2010","journal-title":"Vaccine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.virol.2004.01.031","article-title":"Specific antibodies modulate the interactions of adenovirus type 5 with dendritic cells","volume":"322","author":"Mercier","year":"2004","journal-title":"Virology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1016\/j.vaccine.2014.08.058","article-title":"Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB\/c mice","volume":"32","author":"Kim","year":"2014","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/imm.12462","article-title":"Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus","volume":"145","author":"Guo","year":"2015","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1016\/j.vaccine.2006.11.025","article-title":"Novel adenovirus vaccine vectors based on the enteric-tropic serotype 41","volume":"25","author":"Lemiale","year":"2007","journal-title":"Vaccine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1016\/j.vaccine.2018.04.082","article-title":"Heterologous prime-boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus","volume":"36","author":"Jung","year":"2018","journal-title":"Vaccine"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11603","DOI":"10.1128\/JVI.75.23.11603-11613.2001","article-title":"Replication-defective vector based on a chimpanzee adenovirus","volume":"75","author":"Farina","year":"2001","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1056\/NEJMoa1410863","article-title":"Chimpanzee Adenovirus Vector Ebola Vaccine","volume":"376","author":"Ledgerwood","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1016\/j.vaccine.2017.05.032","article-title":"ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice","volume":"35","author":"Alharbi","year":"2017","journal-title":"Vaccine"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.1128\/IAI.67.9.4780-4786.1999","article-title":"Immunogenicity of DNA vaccines expressing tuberculosis proteins fused to tissue plasminogen activator signal sequences","volume":"67","author":"Li","year":"1999","journal-title":"Infect. Immunity"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1080\/21645515.2015.1042193","article-title":"Effects of the fusion design and immunization route on the immunogenicity of Ag85A-Mtb32 in adenoviral vectored tuberculosis vaccine","volume":"11","author":"Zhang","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41541-017-0029-1","article-title":"Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model","volume":"2","author":"Munster","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1016\/j.vaccine.2007.01.064","article-title":"Attenuated measles virus as a vaccine vector","volume":"25","author":"Zuniga","year":"2007","journal-title":"Vaccine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"11654","DOI":"10.1128\/JVI.01815-15","article-title":"A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform","volume":"89","author":"Malczyk","year":"2015","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virol.2018.05.028","article-title":"Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model","volume":"521","author":"Bodmer","year":"2018","journal-title":"Virology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Kim, S.H., and Samal, S.K. (2016). Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines. Viruses, 8.","DOI":"10.3390\/v8070183"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/S2095-3119(17)61660-5","article-title":"Newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels","volume":"16","author":"Liu","year":"2017","journal-title":"J. Integr. Agric."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molmed.2004.03.003","article-title":"Vesicular stomatitis virus: Re-inventing the bullet","volume":"10","author":"Lichty","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.antiviral.2017.12.007","article-title":"A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization","volume":"150","author":"Liu","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"S414","DOI":"10.1093\/infdis\/jiv251","article-title":"Preclinical Development of Inactivated Rabies Virus-Based Polyvalent Vaccine Against Rabies and Filoviruses","volume":"212","author":"Willet","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e02040-16","DOI":"10.1128\/JVI.02040-16","article-title":"One-Health: A Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus","volume":"91","author":"Wirblich","year":"2017","journal-title":"J. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12033-012-9598-4","article-title":"Construction and characterization of virus-like particles: A review","volume":"53","author":"Zeltins","year":"2013","journal-title":"Mol. Biotechnol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"12686","DOI":"10.18632\/oncotarget.8475","article-title":"MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.antiviral.2016.12.019","article-title":"Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice","volume":"140","author":"Wang","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12201","DOI":"10.1128\/JVI.06048-11","article-title":"A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge","volume":"85","author":"Bolles","year":"2011","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1080\/21645515.2016.1177688","article-title":"Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus","volume":"12","author":"Agrawal","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41426-018-0056-7","article-title":"Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus","volume":"7","author":"Deng","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1128\/JVI.00983-14","article-title":"Effects of Toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB\/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine","volume":"88","author":"Uda","year":"2014","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1038\/nm1209","article-title":"Vaccines: Past, present and future","volume":"11","author":"Plotkin","year":"2005","journal-title":"Nat. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3390\/v4030363","article-title":"The coronavirus E protein: Assembly and beyond","volume":"4","author":"Ruch","year":"2012","journal-title":"Viruses"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"7721","DOI":"10.1128\/JVI.00304-08","article-title":"A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters","volume":"82","author":"Lamirande","year":"2008","journal-title":"J. Virol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e00650-13","DOI":"10.1128\/mBio.00650-13","article-title":"Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate","volume":"4","author":"Almazan","year":"2013","journal-title":"mBio"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1038\/nm.2972","article-title":"A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease","volume":"18","author":"Graham","year":"2012","journal-title":"Nat. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/ni.1979","article-title":"Ribose 2\u2032-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5","volume":"12","author":"Zust","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1128\/JVI.03571-13","article-title":"Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2\u2032-o-methyltransferase activity","volume":"88","author":"Menachery","year":"2014","journal-title":"J. Virol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e00710-18","DOI":"10.1128\/JVI.00710-18","article-title":"Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines","volume":"92","author":"Menachery","year":"2018","journal-title":"J. Virol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e00346-17","DOI":"10.1128\/mSphere.00346-17","article-title":"Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis","volume":"2","author":"Menachery","year":"2017","journal-title":"mSphere"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.antiviral.2014.06.013","article-title":"Accessory proteins of SARS-CoV and other coronaviruses","volume":"109","author":"Liu","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Menachery, V.D., Mitchell, H.D., Cockrell, A.S., Gralinski, L.E., Yount, B.L., Graham, R.L., McAnarney, E.T., Douglas, M.G., Scobey, T., and Beall, A. (2017). MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis. mBio, 8.","DOI":"10.1128\/mBio.00665-17"},{"key":"ref_130","unstructured":"World Health Organization (2003). Consensus Document on the Epidemiology of Severe Acute Respiratory Syndrome (SARS), World Health Organization."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.micinf.2014.05.002","article-title":"Calling for rapid development of a safe and effective MERS vaccine","volume":"16","author":"Hotez","year":"2014","journal-title":"Microbes Infect."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3389\/fimmu.2018.00205","article-title":"Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques","volume":"9","author":"Prescott","year":"2018","journal-title":"Front. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/1\/74\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:26:41Z","timestamp":1760185601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/1\/74"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,17]]},"references-count":132,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["v11010074"],"URL":"https:\/\/doi.org\/10.3390\/v11010074","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,17]]}}}