{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:38:08Z","timestamp":1789184288490,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ab&amp;B Bio-tech Co., Ltd. JS"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Influenza is a serious contagious disease caused by influenza virus. It is particularly dangerous for children, potentially leading to severe and even fatal complications. The aim of this study was to evaluate the safety and immunogenicity of two candidate quadrivalent influenza subunit vaccines in children aged 6\u201335 months. Methods: The subjects were randomly divided into three groups at a 1:1:1 ratio and received the corresponding vaccines: QIV-Sub-HD (Quadrivalent Influenza Subunit Vaccine, High Dose), QIV-Sub-LD (Quadrivalent Influenza Subunit Vaccine, Low Dose) and QIV-Split-LD (Quadrivalent Influenza Split-Virion Vaccine, Low Dose). Adverse events were recorded at 30 min, 0\u20137 days and 8\u201328 and 30 days after each dose of immunization. Serious adverse events (SAEs) were collected and reported within 6 months after the full vaccination. Blood samples were collected before the first dose and on 28 days, 3 months and 6 months after full vaccination for antibody detection to evaluate the immunogenicity and duration of immune responses. Results: The results showed that the relative and absolute criteria met the goals set by the clinical trial protocol, indicating that both vaccines are immunogenic. From the first dose to 30 days after full vaccination, the total incidence of adverse reactions in the QIV-Sub-HD, QIV-Sub-LD and QIV-Split-LD groups was 29.64%, 33.33% and 29.64%, respectively. The main symptoms were fever, cough, diarrhea and vomiting. No new safety concerns were identified. Conclusions: The quadrivalent influenza subunit vaccines candidate, manufactured by Ab&amp;B Bio-tech Co., Ltd. JS., are safe and immunogenic in children aged 6\u201335 months.<\/jats:p>","DOI":"10.3390\/vaccines13050467","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:00:39Z","timestamp":1745917239000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Safety and Immunogenicity of a Quadrivalent Influenza Subunit Vaccine in Healthy Children Aged 6\u201335 Months: A Randomized, Blinded and Positive-Controlled Phase III Clinical Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Lili","family":"Huang","sequence":"first","affiliation":[{"name":"Henan Provincial Centre for Disease Control and Prevention, Zhengzhou 450016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfu","family":"Li","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Provincial Centre for Disease Control and Prevention, Zhengzhou 450016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiebing","family":"Tan","sequence":"additional","affiliation":[{"name":"Henan Provincial Centre for Disease Control and Prevention, Zhengzhou 450016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofen","family":"Chen","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"An","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenna","family":"Leng","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcai","family":"An","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Provincial Centre for Disease Control and Prevention, Zhengzhou 450016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaodong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ab&B Bio-Tech Co., Ltd. JS, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/QCO.0b013e3280ad4687","article-title":"The burden of influenza in children","volume":"20","author":"Iskander","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7524","DOI":"10.1016\/j.vaccine.2011.08.010","article-title":"Seasonal influenza: The burden of disease in children","volume":"29","author":"Fraaij","year":"2011","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Committee on Infectious Diseases (2022). Recommendations for Prevention and Control of Influenza in Children, 2022\u20132023. Pediatrics, 150, e2022059275.","DOI":"10.1542\/peds.2022-059274"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3949\/ccjm.87a.20161","article-title":"COVID-19 and flu: Dual threat, dual opportunity","volume":"87","author":"Mossad","year":"2020","journal-title":"Cleve Clin. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.idc.2017.11.005","article-title":"Updates on Influenza Vaccination in Children","volume":"32","author":"Campbell","year":"2018","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_6","unstructured":"National Immunization Advisory Committee (NIAC) Technical Working Group (TWG), and Influenza Vaccination TWG (2023). [Technical guidelines for seasonal influenza vaccination in China (2023\u20132024)]. Zhonghua Liu Xing Bing Xue Za Zhi, 44, 1507\u20131530."},{"key":"ref_7","first-page":"2241","article-title":"Influenza sentinel surveillance report in Republic of Korea, 2019\u20132020","volume":"12","author":"Cheun","year":"2019","journal-title":"PHWR Public Health Wkly. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/emph\/eoy013","article-title":"The continual threat of influenza virus infections at the human-animal interface: What is new from a one health perspective?","volume":"2018","author":"Bailey","year":"2018","journal-title":"Evol. Med. Public Health."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.2105\/AJPH.2012.301137","article-title":"The burden of influenza B: A structured literature review","volume":"103","author":"Schmier","year":"2013","journal-title":"Am. J. Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D45","DOI":"10.1016\/j.vaccine.2010.08.028","article-title":"The need for quadrivalent vaccine against seasonal influenza","volume":"28","author":"Belshe","year":"2010","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e20154643","DOI":"10.1542\/peds.2015-4643","article-title":"Hospitalization for Influenza A Versus B","volume":"138","author":"Tran","year":"2016","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Webster, R.G., Monto, A.S., Braciale, T.J., and Lamb, R.A. (2013). Textbook of Influenza, John Wiley & Sons, Ltd.. [2nd ed.].","DOI":"10.1002\/9781118636817"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1016\/j.vaccine.2018.04.063","article-title":"Estimating the annual attack rate of seasonal influenza among unvaccinated individuals: A systematic review and meta-analysis","volume":"36","author":"Somes","year":"2018","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1016\/j.vaccine.2012.04.057","article-title":"Indirect, out-of-pocket and medical costs from influenza-related illness in young children","volume":"30","author":"Molinari","year":"2012","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Antonova, E.N., Rycroft, C.E., Ambrose, C.S., Heikkinen, T., and Principi, N. (2012). Burden of paediatric influenza in Western Europe: A systematic review. BMC Public Health, 12.","DOI":"10.1186\/1471-2458-12-968"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5086","DOI":"10.1016\/j.vaccine.2007.03.046","article-title":"The annual impact of seasonal influenza in the US: Measuring disease burden and costs","volume":"25","author":"Molinari","year":"2007","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/irv.12604","article-title":"The impact of influenza infection on young children, their family and the health care system","volume":"13","author":"Willis","year":"2019","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40249-015-0077-6","article-title":"The economic burden of influenza-associated outpatient visits and hospitalizations in China: A retrospective survey","volume":"4","author":"Yang","year":"2015","journal-title":"Infect. Dis. Poverty"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ijid.2020.02.040","article-title":"Who and when to vaccinate against influenza","volume":"93","author":"Buchy","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1016\/j.vaccine.2022.02.088","article-title":"Efficacy and safety of a quadrivalent influenza vaccine in children aged 6-35 months: A global, multiseasonal, controlled, randomized Phase III study","volume":"40","author":"Esposito","year":"2022","journal-title":"Vaccine"},{"key":"ref_21","unstructured":"(2012). Vaccines against influenza WHO position paper\u2013November 2012. Wkly. Epidemiol. Rec., 87, 461\u2013476."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/irv.12318","article-title":"Retrospective public health impact of a quadrivalent influenza vaccine in the United States","volume":"9","author":"Postma","year":"2015","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1093\/cid\/ciu664","article-title":"Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999\u20132012","volume":"59","author":"Heikkinen","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","unstructured":"Yang, X.M., Gao, F., Yu, Y.X., Wei, Y., Xiong, S., Wang, J., Li, Z., Xu, D., and Huang, S. (2020). A New Generation of Vaccine, Higher Education Press. [2nd ed.]."},{"key":"ref_25","first-page":"570","article-title":"[Comparative study on safety and immunogenicity between influenza subunit vaccine and split vaccine]","volume":"24","author":"Dong","year":"2003","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1016\/j.vaccine.2021.05.070","article-title":"Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized, double-blind, active-controlled phase 1 clinical trial","volume":"39","author":"Wang","year":"2021","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21645515.2021.1885278","article-title":"Immunogenicity and safety of two quadrivalent influenza vaccines in healthy adult and elderly participants in India - A phase III, active-controlled, randomized clinical study","volume":"18","author":"Basu","year":"2022","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_28","unstructured":"Cherry, J.D., Harrison, G.J., Kaplan, S.L., Steinbach, W.J., and Hotez, P.J. (2019). Influenza Viruses. Feigin and Cherry\u2019s Textbook of Pediatric Infectious Diseases, Elsevier."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2132798","DOI":"10.1080\/21645515.2022.2132798","article-title":"Immunological non-inferiority and safety of a quadrival-ent inactivated influenza vaccine versus two trivalent inactivated influenza vaccines in China: Results from two studies","volume":"18","author":"Liu","year":"2022","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/INF.0000000000002227","article-title":"Safety and Immunogenicity of a Full-dose, Split-virion, Inactivated, Quadrivalent Influenza Vaccine in Healthy Children 6-35 Months of Age: A Randomized Controlled Clinical Trial","volume":"38","author":"Robertson","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4933","DOI":"10.1016\/j.vaccine.2022.06.078","article-title":"Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects \u22653 years: A randomized, multicenter, double-blind, active-controlled phase III, non-inferiority trial","volume":"40","author":"Zhang","year":"2022","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1080\/21645515.2020.1721994","article-title":"Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III clinical trial in children aged 6\u201335 months in China","volume":"16","author":"Hu","year":"2020","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_33","first-page":"9","article-title":"Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial","volume":"6","author":"Jain","year":"2017","journal-title":"J. Pediatr. Infect. Dis. Soc."}],"updated-by":[{"DOI":"10.3390\/vaccines13080826","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000}}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/5\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:22:21Z","timestamp":1754648541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/5\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,26]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["vaccines13050467"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13050467","relation":{"correction":[{"id-type":"doi","id":"10.3390\/vaccines13080826","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,26]]}}}