{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:08:12Z","timestamp":1792699692411,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["RIA2017S-2027"],"award-info":[{"award-number":["RIA2017S-2027"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1205877"],"award-info":[{"award-number":["OPP1205877"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of &gt;100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV\u00ae, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified\/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).<\/jats:p>","DOI":"10.3390\/vaccines9030281","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T23:47:41Z","timestamp":1616370461000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-0011","authenticated-orcid":false,"given":"Andrea Haekyung","family":"Haselbeck","sequence":"first","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4005-8605","authenticated-orcid":false,"given":"Birkneh Tilahun","family":"Tadesse","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyeon","family":"Park","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"},{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-0053","authenticated-orcid":false,"given":"Malick M.","family":"Gibani","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College of Medicine, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-4723","authenticated-orcid":false,"given":"Ligia Mar\u00eda Cruz","family":"Espinoza","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-0991","authenticated-orcid":false,"given":"Ariane","family":"Abreu","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Van Rensburg","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-0564","authenticated-orcid":false,"given":"Michael","family":"Owusu-Ansah","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampson","family":"Twuamsi-Ankrah","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Owusu","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Aguna","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Picot","sequence":"additional","affiliation":[{"name":"Fondation M\u00e9rieux, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-4574","authenticated-orcid":false,"given":"Hyonjin","family":"Jeon","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"},{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Higginson","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunju","family":"Park","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenaida R.","family":"Mojares","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Im","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Carey","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Khanam","sequence":"additional","affiliation":[{"name":"International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Tonks","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Dougan","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deokryun","family":"Kim","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Seattle Epidemiologic Research and Information Center, Cooperative Studies Program, Office of Research and Development, United States Department of Veterans Affairs, Seattle, WA 98174, USA"},{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"},{"name":"Department of Epidemiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-8072","authenticated-orcid":false,"given":"Vittal","family":"Mogasale","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Neuzil","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdausi","family":"Qadri","sequence":"additional","affiliation":[{"name":"International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-1534","authenticated-orcid":false,"given":"Yaw","family":"Adu-Sarkodie","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis","family":"Owusu-Dabo","sequence":"additional","affiliation":[{"name":"School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi 00000, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Clemens","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"},{"name":"International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh"},{"name":"Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-7170","authenticated-orcid":false,"given":"Florian","family":"Marks","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul 08826, Korea"},{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge CB2 0SL, UK"},{"name":"Laboratory of Microbiology and Parasitology, University of Antananarivo, Antananarivo 566, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 (2019). Typhoid and Paratyphoid Collaborators, The global burden of typhoid and paratyphoid fevers: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect. Dis., 19, 369\u2013381."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"John, J., Van Aart, C.J.C., and Grassly, N.C. (2016). The Burden of Typhoid and Paratyphoid in India: Systematic Review and Meta-analysis. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004616"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Buckle, G.C., Walker, C.L., and Black, R.E. (2012). Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010. J. Glob. Health, 2.","DOI":"10.7189\/jogh.01.010401"},{"key":"ref_4","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e570","DOI":"10.1016\/S2214-109X(14)70301-8","article-title":"Burden of typhoid fever in low-income and middle-income countries: A systematic, literature-based update with risk-factor adjustment","volume":"2","author":"Mogasale","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e310","DOI":"10.1016\/S2214-109X(17)30022-0","article-title":"Incidence of invasive Salmonella disease in sub-Saharan Africa: A multicentre population-based surveillance study","volume":"5","author":"Marks","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S417","DOI":"10.1093\/cid\/ciz629","article-title":"How Can. the Typhoid Fever Surveillance in Africa and the Severe Typhoid Fever in Africa Programs Contribute to the Introduction of Typhoid Conjugate Vaccines?","volume":"69","author":"Jeon","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Parry, C.M., Ribeiro, I., Walia, K., Rupali, P., Baker, S., and Basnyat, B. (2019). Multidrug resistant enteric fever in South. Asia: Unmet medical needs and opportunities. BMJ, 364.","DOI":"10.1136\/bmj.k5322"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1353\/dem.2005.0002","article-title":"The role of public health improvements in health advances: The twentieth-century United States","volume":"42","author":"Cutler","year":"2005","journal-title":"Demography"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lee, J.-S., Mogasale, V.V., Mogasale, V., and Lee, K. (2016). Geographical distribution of typhoid risk factors in low and middle income countries. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-2074-1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Im, J., Islam, M.T., Ahmmed, F., Kim, D.R., Khan, A.I., Zaman, K., Ali, M., Marks, F., Qadri, F., and Kim, J. (2020). Can existing improvements of water, sanitation, and hygiene (WASH) in urban slums reduce the burden of typhoid fever in these settings?. Clin. Infect. Dis.","DOI":"10.1093\/cid\/ciaa1429"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"World Health Oorganization (2019). Typhoid vaccines: WHO position paper, March 2018, Recommendations. Vaccine, 37, 214\u2013216.","DOI":"10.1016\/j.vaccine.2018.04.022"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1016\/j.vaccine.2020.03.028","article-title":"Adverse events following immunization with typhoid conjugate vaccine in an outbreak setting in Hyderabad, Pakistan","volume":"38","author":"Qamar","year":"2020","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1473-3099(13)70241-X","article-title":"Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: Results from two randomised, observer-blind, age de-escalation, phase 2 trials","volume":"14","author":"Bhutta","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5806","DOI":"10.1128\/IAI.67.11.5806-5810.1999","article-title":"Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam","volume":"67","author":"Kossaczka","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Capeding, M.R., Sil, A., Tadesse, B.T., Saluja, T., Teshome, S., Alberto, E., Kim, D.R., Park, E.L., Park, J.Y., and Yang, J.S. (2020). Safety and immunogenicity of Vi-D conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study. EClinicalMedicine, 27.","DOI":"10.1016\/j.eclinm.2020.100540"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1016\/j.vaccine.2019.09.074","article-title":"Immunogenicity, safety and reactogenicity of a Phase II trial of Vi-DT typhoid conjugate vaccine in healthy Filipino infants and toddlers: A preliminary report","volume":"38","author":"Capeding","year":"2020","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S155","DOI":"10.1093\/cid\/ciaa370","article-title":"Early Insights From Clinical Trials of Typhoid Conjugate Vaccine","volume":"71","author":"Neuzil","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1905047","article-title":"Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal","volume":"381","author":"Shakya","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1093\/cid\/ciy1107","article-title":"Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infection Among Bangladeshi Children: A Protocol for a Phase IIIb Trial","volume":"68","author":"Qadri","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S1473-3099(10)70318-2","article-title":"New approaches to the assessment of vaccine herd protection in clinical trials","volume":"11","author":"Clemens","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","unstructured":"Sabin Vaccine Institute (2017, January 4\u20136). Public health experts discuss vaccines, antibiotic resistance and surveillance. Proceedings of the 10th International Conference on Typhoid and Other Invasive Salmonelloses, Pin Kampala, Uganda."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S422","DOI":"10.1093\/cid\/ciz715","article-title":"The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess. Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis","volume":"69","author":"Park","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pak, G.D., Haselback, A.H., Seo, H.W., Osei, I., Amuasi, J., Breiman, R.F., Espinosa, L.M.C., Holm, M., Im, J., and Jang, G.H. (2018). The HPAfrica protocol: Assessment of health behaviour and population-based socioeconomic, hygiene behavioural factors\u2014A standardised repeated cross-sectional study in multiple cohorts in sub-Saharan Africa. BMJ Open, 8.","DOI":"10.1136\/bmjopen-2017-021438"},{"key":"ref_25","unstructured":"Hayes, R.J., and Moulton, L.H. (2017). Cluster Randomised Trials, Chapman and Hall\/CRC. [2nd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1445-2197.2009.04994.x","article-title":"Estimating the risk of rare complications: Is the \u2018rule of three\u2019 good enough?","volume":"79","author":"Ludbrook","year":"2009","journal-title":"ANZ J. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Harris, P.A., Taylor, R., Minor, B.L., Elliott, V., Fernandez, M., O\u2019Neal, L., McLeod, L., Delacqua, G., Kirby, J., and Duda, S.N. (2019). The REDCap consortium: Building an international community of software platform partners. J. Biomed. Inform., 95.","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S172","DOI":"10.1093\/cid\/ciaa597","article-title":"Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018","volume":"71","author":"Date","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","unstructured":"World Health Organization (2019). WHO Guide for Standardization of Economic Evaluations of Immunization Programmes, World Health Organization. [2nd ed.]. Licence: CC BY-NC-SA 3.0IGO."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S459","DOI":"10.1093\/cid\/ciz608","article-title":"A Multicenter Cost-of-Illness and Long-term Socioeconomic Follow-up Study in the Severe Typhoid Fever in Africa Program: Study Protocol","volume":"69","author":"Ramani","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/cid\/cix1145","article-title":"Seroefficacy of Vi Polysaccharide-Tetanus Toxoid Typhoid Conjugate Vaccine (Typbar TCV)","volume":"67","author":"Voysey","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","unstructured":"Neuzil, K.M. (2020). More Typhoid Conjugate Vaccines, More Impact, Available online: https:\/\/www.coalitionagainsttyphoid.org\/moretyphoidconjugatevaccines\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1016\/j.vaccine.2018.05.038","article-title":"Safety and immunogenicity of a Vi-DT typhoid conjugate vaccine: Phase I trial in Healthy Filipino adults and children","volume":"36","author":"Capeding","year":"2018","journal-title":"Vaccine"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:38:25Z","timestamp":1760161105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,19]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["vaccines9030281"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9030281","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,19]]}}}