{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:19:52Z","timestamp":1789057192781,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human rhinoviruses (HRVs) are small non-enveloped RNA viruses that belong to the Enterovirus genus within the Picornaviridae family and are known for causing the common cold. Though symptoms are generally mild in healthy individuals, the economic burden associated with HRV infection is significant. A vaccine could prevent disease. The Vero-cell-based viral vaccine platform technology was considered for such vaccine development. Unfortunately, most HRV strains are unable to propagate on Vero cells due to a lack of the major receptor of HRV group A and B, intercellular adhesion molecule (ICAM1, also known as CD54). Therefore, stable human ICAM1 expressing Vero cell clones were generated by transfecting the ICAM1 gene in Vero cells and selecting clones that overexpressed ICAM1 on the cell surface. Cell banks were made and expression of ICAM1 was stable for at least 30 passages. The Vero_ICAM1 cells and parental Vero cells were infected with four HRV prototypes, B14, A16, B37 and A57. Replication of all four viruses was detected in Vero_ICAM1, but not in the parental Vero cells. Altogether, Vero cells expressing ICAM1 could efficiently propagate the tested HRV strains. Therefore, ICAM1-expressing cells could be a useful tool for the development and future production of polyvalent HRV vaccines or other viruses that use ICAM1 as a receptor.<\/jats:p>","DOI":"10.3390\/v14102235","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:31:18Z","timestamp":1665552678000},"page":"2235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Construction of a Vero Cell Line Expressing Human ICAM1 for the Development of Rhinovirus Vaccines"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6170-9051","authenticated-orcid":false,"given":"Wouter Johannes Petrus","family":"van den Braak","sequence":"first","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Monica","sequence":"additional","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5667-5440","authenticated-orcid":false,"given":"Diana","family":"Limpens","sequence":"additional","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dedeke","family":"Rockx-Brouwer","sequence":"additional","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijn","family":"de Boer","sequence":"additional","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8707-2266","authenticated-orcid":false,"given":"Dinja","family":"Oosterhoff","sequence":"additional","affiliation":[{"name":"Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","unstructured":"(2022, September 07). Taxonomy, International Committee on Taxonomy of Viruses. Available online: https:\/\/ictv.global\/taxonomy."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/317145a0","article-title":"Structure of a human common cold virus and functional relationship to other picornaviruses","volume":"317","author":"Rossmann","year":"1985","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1128\/jvi.57.1.246-257.1986","article-title":"Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14","volume":"57","author":"Sherry","year":"1986","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bartlett, N., Wark, P., and Knight, D. (2019). Chapter 1\u2014Rhinovirus structure, replication, and classification. Rhinovirus Infections, Academic Press.","DOI":"10.1016\/B978-0-12-816417-4.00001-9"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJM196612082752301","article-title":"Rhinovirus infections in an industrial population. I. The occurrence of illness","volume":"275","author":"Gwaltney","year":"1966","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jaci.2004.09.025","article-title":"The September epidemic of asthma exacerbations in children: A search for etiology","volume":"115","author":"Johnston","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1136\/bmj.310.6989.1225","article-title":"Community study of role of viral infections in exacerbations of asthma in 9\u201311 year old children","volume":"310","author":"Johnston","year":"1995","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1164\/ajrccm.164.9.2105011","article-title":"Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease","volume":"164","author":"Seemungal","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1164\/rccm.200506-859OC","article-title":"Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations","volume":"173","author":"Papi","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1001\/archinte.163.4.487","article-title":"The economic burden of non-influenza-related viral respiratory tract infection in the United States","volume":"163","author":"Fendrick","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1126\/science.3018924","article-title":"The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating","volume":"233","author":"Smith","year":"1986","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S1473-3099(02)00277-3","article-title":"FDA panel rejects common cold treatment","volume":"2","author":"Senior","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1128\/AAC.47.12.3907-3916.2003","article-title":"Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers","volume":"47","author":"Hayden","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1128\/AAC.01175-13","article-title":"A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIbeta","volume":"57","author":"Leyssen","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41557-018-0039-2","article-title":"Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus","volume":"10","author":"Mousnier","year":"2018","journal-title":"Nat. Chem."},{"key":"ref_16","unstructured":"Bartlett, N., Wark, P., and Knight, D. (2019). Chapter 9\u2014Emerging therapeutic approaches. Rhinovirus Infections, Academic Press."},{"key":"ref_17","unstructured":"WHO (2022, September 09). Two Out of Three Wild Poliovirus Strains Eradicated. Available online: https:\/\/www.who.int\/news-room\/feature-stories\/detail\/two-out-of-three-wild-poliovirus-strains-eradicated."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/infdis\/151.3.420","article-title":"Oral poliovirus vaccine: History of its development and use and current challenge to eliminate poliomyelitis from the world","volume":"151","author":"Sabin","year":"1985","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1586\/14760584.2016.1138862","article-title":"EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD)","volume":"15","author":"Mao","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/rmv.1827","article-title":"Comparative epidemiology and virology of fatal and nonfatal cases of hand, foot and mouth disease in mainland China from 2008 to 2014","volume":"25","author":"Liu","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Guo, W., Xu, D., Cong, S., Du, Z., Li, L., Zhang, M., Feng, C., Bao, G., Sun, H., and Yang, Z. (2022). Co-infection and enterovirus B: Post EV-A71 mass vaccination scenario in China. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07661-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1016\/j.vaccine.2018.05.005","article-title":"The immunogenicity and protection effect of an inactivated coxsackievirus A6, A10, and A16 vaccine against hand, foot, and mouth disease","volume":"36","author":"Lim","year":"2018","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1080\/22221751.2022.2093132","article-title":"Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils","volume":"11","author":"Sun","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.vaccine.2020.11.070","article-title":"Efficacy of an inactivated bivalent vaccine for enterovirus 71 and coxsackievirus A16 in mice immunized intradermally","volume":"39","author":"Fan","year":"2021","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7095","DOI":"10.1016\/j.vaccine.2018.09.069","article-title":"Characterization of an inactivated whole-virus bivalent vaccine that induces balanced protective immunity against coxsackievirus A6 and A10 in mice","volume":"36","author":"Zhang","year":"2018","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000065866","article-title":"Human rhinovirus 87 identified as human enterovirus 68 by VP4-based molecular diagnosis","volume":"45","author":"Ishiko","year":"2002","journal-title":"Intervirology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1473-3099(15)70093-9","article-title":"A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012\u20132014): A retrospective cohort study","volume":"15","author":"Greninger","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00284-20","DOI":"10.1128\/JCM.00284-20","article-title":"Biennial Upsurge and Molecular Epidemiology of Enterovirus D68 Infection in New York, USA, 2014 to 2018","volume":"58","author":"Gilrane","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.vaccine.2017.12.057","article-title":"A virus-like particle vaccine confers protection against enterovirus D68 lethal challenge in mice","volume":"36","author":"Dai","year":"2018","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhang, C., Zhang, X., Dai, W., Liu, Q., Xiong, P., Wang, S., Geng, L., Gong, S., and Huang, Z. (2018). A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses, 10.","DOI":"10.3390\/v10020058"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaba4902","DOI":"10.1126\/sciimmunol.aba4902","article-title":"Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease","volume":"5","author":"Vogt","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4049\/jimmunol.108.1.169","article-title":"Further characterization of the local respiratory tract antibody response induced by intranasal instillation of inactivated rhinovirus 13 vaccine","volume":"108","author":"Buscho","year":"1972","journal-title":"J. Immunol."},{"key":"ref_33","first-page":"727","article-title":"Demonstration and characterization of antibody in tears following intranasal vaccination with inactivated type 13 rhinovirus: A preliminary report","volume":"9","author":"Knopf","year":"1970","journal-title":"Investig. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4049\/jimmunol.104.3.566","article-title":"Analysis of the neutralizing activity in nasal wash and serum following intranasal vaccinaion with inactivated type 13 rhinovirus","volume":"104","author":"Knopf","year":"1970","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/oxfordjournals.aje.a121076","article-title":"Evidence for protective effect of an inactivated rhinovirus vaccine administered by the nasal route","volume":"90","author":"Perkins","year":"1969","journal-title":"Am. J. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/infdis\/132.6.623","article-title":"Human responses to two decavalent rhinovirus vaccines","volume":"132","author":"Hamory","year":"1975","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12838","DOI":"10.1038\/ncomms12838","article-title":"A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques","volume":"7","author":"Lee","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.coviro.2015.03.004","article-title":"Challenges in developing a cross-serotype rhinovirus vaccine","volume":"11","author":"Glanville","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/biot.201400388","article-title":"Designing cell lines for viral vaccine production: Where do we stand?","volume":"10","author":"Genzel","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_40","first-page":"97","article-title":"Human diploid cell strains (HDCS) viral vaccines","volume":"93","author":"Fletcher","year":"1998","journal-title":"Dev. Biol. Stand."},{"key":"ref_41","first-page":"1201","article-title":"Studies on SV40 in tissue culture-preliminary step for cancer research in vitro","volume":"21","author":"Yasumura","year":"1963","journal-title":"Nihon Rinsho"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"670","DOI":"10.3181\/00379727-132-34285","article-title":"Biological characteristics and viral susceptibility of an African green monkey kidney cell line (Vero)","volume":"132","author":"Rhim","year":"1969","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_43","first-page":"27","article-title":"Polio and rabies vaccines produced in continuous cell lines: A reality for Vero cell line","volume":"70","author":"Montagnon","year":"1989","journal-title":"Dev. Biol. Stand."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S341","DOI":"10.1093\/clinids\/6.Supplement_2.S341","article-title":"Industrial-scale production of inactivated poliovirus vaccine prepared by culture of Vero cells on microcarrier","volume":"6","author":"Montagnon","year":"1984","journal-title":"Rev. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1586\/erv.09.19","article-title":"Vero cell platform in vaccine production: Moving towards cell culture-based viral vaccines","volume":"8","author":"Barrett","year":"2009","journal-title":"Expert Rev. Vaccines"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0140-6736(10)62228-3","article-title":"Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: A multicentre, double-blind, randomised, placebo-controlled trial","volume":"377","author":"Barrett","year":"2011","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/14760584.2017.1357471","article-title":"Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases","volume":"16","author":"Barrett","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/0092-8674(89)90689-2","article-title":"A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses","volume":"56","author":"Staunton","year":"1989","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/S0891-5849(00)00223-9","article-title":"Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades","volume":"28","author":"Hubbard","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1099\/vir.0.19329-0","article-title":"Cellular receptor interactions of C-cluster human group A coxsackieviruses","volume":"84","author":"Newcombe","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.chom.2016.09.013","article-title":"ICAM-5\/Telencephalin Is a Functional Entry Receptor for Enterovirus D68","volume":"20","author":"Wei","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1073\/pnas.86.13.4907","article-title":"cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1","volume":"86","author":"Tomassini","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1073\/pnas.1421178112","article-title":"Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication","volume":"112","author":"Bochkov","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13636","DOI":"10.1073\/pnas.0403998101","article-title":"A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice","volume":"101","author":"Dufresne","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1073\/pnas.1713284115","article-title":"Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus","volume":"115","author":"Baggen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000149850","article-title":"Enterovirus etiology of the 1970 Singapore epidemic of acute conjunctivitis","volume":"4","author":"Mirkovic","year":"1974","journal-title":"Intervirology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/rmv.457","article-title":"Role of recombination in evolution of enteroviruses","volume":"15","author":"Lukashev","year":"2005","journal-title":"Rev. Med. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2147\/OV.S56322","article-title":"Applications of coxsackievirus A21 in oncology","volume":"3","author":"Bradley","year":"2014","journal-title":"Oncolytic Virother."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hwang, J.K., Hong, J., and Yun, C.O. (2020). Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228627"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:26Z","timestamp":1760143826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":60,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["v14102235"],"URL":"https:\/\/doi.org\/10.3390\/v14102235","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}