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Compared with other countries, China has a large population base and a large number of influenza cases and deaths. Currently, influenza vaccination remains the most cost-effective and efficient way to prevent and control influenza, which can significantly reduce the risk of influenza virus infection and serious complications. The antigenicity of the influenza vaccine exhibits good protective efficacy when matched to the seasonal epidemic strain. However, when influenza viruses undergo rapid and sustained antigenic drift resulting in a mismatch between the vaccine strain and the epidemic strain, the protective effect is greatly reduced. As a result, the flu vaccine must be reformulated and readministered annually, causing a significant drain on human and financial resources. Therefore, the development of a universal influenza vaccine is necessary for the complete fight against the influenza virus. By statistically analyzing cases related to influenza virus infection and death in China in recent years, this paper describes the existing marketed vaccines, vaccine distribution and vaccination in China and summarizes the candidate immunogens designed based on the structure of influenza virus, hoping to provide ideas for the design and development of new influenza vaccines in the future.<\/jats:p>","DOI":"10.3390\/v15010116","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:12:48Z","timestamp":1672625568000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Influenza and Universal Vaccine Research in China"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5111-740X","authenticated-orcid":false,"given":"Jiali","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-0035","authenticated-orcid":false,"given":"Longding","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.tim.2018.05.013","article-title":"Influenza Virus","volume":"26","author":"Hutchinson","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_2","first-page":"E64","article-title":"The Spanish Influenza Pandemic: A lesson from history 100 years after 1918","volume":"60","author":"Martini","year":"2019","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3906\/sag-2004-133","article-title":"Understanding dynamics of pandemics","volume":"50","author":"Akin","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/bmb\/ldz036","article-title":"Avian influenza viruses in humans: Lessons from past outbreaks","volume":"132","author":"Li","year":"2019","journal-title":"Br. Med. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Eladl, A.H., Farag, V.M., El-Shafei, R.A., Aziza, A.E., Awadin, W.F., and Arafat, N. (2022). Immunological, biochemical and pathological effects of vitamin C and Arabic gum co-administration on H9N2 avian influenza virus vaccinated and challenged laying Japanese quails. BMC Veter Res., 18.","DOI":"10.1186\/s12917-022-03495-y"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.vetmic.2013.09.022","article-title":"Antigenic analysis of H5N1 highly pathogenic avian influenza viruses circulating in Egypt (2006\u20132012)","volume":"167","author":"Ibrahim","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.vetmic.2012.10.007","article-title":"Enhanced replication of swine influenza viruses in dexamethasone-treated juvenile and layer turkeys","volume":"162","author":"Ali","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1146\/annurev-med-120617-041310","article-title":"Is a Universal Influenza Virus Vaccine Possible?","volume":"71","author":"Nachbagauer","year":"2020","journal-title":"Annu. Rev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, J., Nian, X., Li, X., Huang, S., Duan, K., Li, X., and Yang, X. (2022). The Epidemiology of Influenza and the Associated Vaccines Development in China: A Review. Vaccines, 10.","DOI":"10.3390\/vaccines10111873"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Diamond, C., Gong, H., Sun, F.Y., Liu, Y., Quilty, B.J., Jit, M., Yang, J., Yu, H., Edmunds, W.J., and Baguelin, M. (2022). Regional-based within-year seasonal variations in influenza-related health outcomes across mainland China: A systematic review and spatio-temporal analysis. BMC Med., 20.","DOI":"10.1186\/s12916-022-02269-5"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/irv.12711","article-title":"Burden of influenza-associated outpatient influenza-like illness consultations in China, 2006-2015: A population-based study","volume":"14","author":"Feng","year":"2020","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_12","first-page":"560","article-title":"Estimating the disease burden of seasonal influenza in China, 2006\u20132019","volume":"101","author":"Gong","year":"2021","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e473","DOI":"10.1016\/S2468-2667(19)30163-X","article-title":"Influenza-associated excess respiratory mortality in China, 2010\u20132015: A population-based study","volume":"4","author":"Li","year":"2019","journal-title":"Lancet Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1016\/j.vaccine.2018.05.057","article-title":"Economic burden of seasonal influenza in the United States","volume":"36","author":"Putri","year":"2018","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/jan.13894","article-title":"Can the Health Belief Model and moral responsibility explain influenza vaccination uptake among nurses?","volume":"75","author":"Mo","year":"2019","journal-title":"J. Adv. Nurs."},{"key":"ref_16","first-page":"1356","article-title":"Technical guidelines for seasonal influenza vaccination in China (2022\u20132023)","volume":"56","author":"Peng","year":"2022","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi Chin. J. Prev. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/j.vaccine.2020.01.093","article-title":"Influenza vaccination rate and its association with chronic diseases in China: Results of a national cross-sectional study","volume":"38","author":"Fan","year":"2020","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/21645515.2017.1423157","article-title":"Knowledge, Attitudes and Practices (KAP) toward seasonal influenza vaccine among young workers in South China","volume":"14","author":"Ma","year":"2018","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1080\/21645515.2018.1496767","article-title":"Determinants of healthcare workers\u2019 willingness to recommend the seasonal influenza vaccine to diabetic patients: A cross-sectional survey in Ningbo, China","volume":"14","author":"Ye","year":"2018","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7262","DOI":"10.1016\/j.vaccine.2018.10.045","article-title":"Influenza vaccination coverage of population and the factors influencing influenza vaccination in mainland China: A meta-analysis","volume":"36","author":"Wang","year":"2018","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1016\/j.vaccine.2018.04.060","article-title":"Identifying ways to increase seasonal influenza vaccine uptake among pregnant women in China: A qualitative investigation of pregnant women and their obstetricians","volume":"36","author":"Li","year":"2018","journal-title":"Vaccine"},{"key":"ref_22","first-page":"3","article-title":"Influenza. Nature reviews","volume":"4","author":"Krammer","year":"2018","journal-title":"Dis. Prim."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nuwarda, R.F., Alharbi, A.A., and Kayser, V. (2021). An Overview of Influenza Viruses and Vaccines. Vaccines, 9.","DOI":"10.3390\/vaccines9091032"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2741\/s502","article-title":"Molecular evolution of hemagglutinin gene of Influenza A virus","volume":"10","author":"De","year":"2018","journal-title":"Front. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a038778","DOI":"10.1101\/cshperspect.a038778","article-title":"Influenza Hemagglutinin Structures and Antibody Recognition","volume":"10","author":"Wu","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4149\/av_2020_408","article-title":"Universal anti-influenza vaccines based on viral HA2 and M2e antigens","volume":"64","year":"2020","journal-title":"Acta Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"a028852","DOI":"10.1101\/cshperspect.a028852","article-title":"Is It Possible to Develop a \u201cUniversal\u201d Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination","volume":"10","author":"Angeletti","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"De Vries, R.D., Herfst, S., and Richard, M. (2018). Avian Influenza A Virus Pandemic Preparedness and Vaccine Development. Vaccines, 6.","DOI":"10.3390\/vaccines6030046"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/21645515.2019.1649551","article-title":"A systematic review and meta-analysis of cross-reactivity of antibodies induced by H7 influenza vaccine","volume":"16","author":"Gou","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1089\/vim.2017.0141","article-title":"Influenza Virus: Dealing with a Drifting and Shifting Pathogen","volume":"31","author":"Kim","year":"2018","journal-title":"Viral Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"711997","DOI":"10.3389\/fimmu.2021.711997","article-title":"Advances in Development and Application of Influenza Vaccines","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1089\/ars.2021.0033","article-title":"Influenza A Virus Hemagglutinin Is Produced in Different Disulfide-Bonded States","volume":"35","author":"Chiu","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.vaccine.2020.12.001","article-title":"HA1 (Hemagglutinin) quantitation for influenza A H1N1 and H3N2 high yield reassortant vaccine candidate seed viruses by RP-UPLC","volume":"39","author":"Fulvini","year":"2020","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a038638","DOI":"10.1101\/cshperspect.a038638","article-title":"Hemagglutinin Structure and Activities","volume":"11","author":"Gamblin","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_35","first-page":"195","article-title":"Hemagglutinin consensus-based prophylactic approaches to overcome influenza virus diversity","volume":"55","author":"Sautto","year":"2019","journal-title":"Vet. Ital."},{"key":"ref_36","first-page":"715","article-title":"Emerging and state of the art hemagglutinin-targeted influenza virus inhibitors","volume":"22","author":"Zhang","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Neerukonda, S.N., Vassell, R., and Weiss, C.D. (2020). Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin. Vaccines, 8.","DOI":"10.3390\/vaccines8030382"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41591-020-1118-7","article-title":"A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial","volume":"27","author":"Nachbagauer","year":"2020","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3389\/fmicb.2020.00135","article-title":"Broadly Protective Strategies Against Influenza Viruses: Universal Vaccines and Therapeutics","volume":"11","author":"Vogel","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.coi.2018.04.001","article-title":"Development of next generation hemagglutinin-based broadly protective influenza virus vaccines","volume":"53","author":"Nachbagauer","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00333-19","DOI":"10.1128\/JVI.00333-19","article-title":"Development of Influenza B Universal Vaccine Candidates Using the \u201cMosaic\u201d Hemagglutinin Approach","volume":"93","author":"Sun","year":"2019","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1080\/14760584.2020.1777861","article-title":"Development of broadly reactive influenza vaccines by targeting the conserved regions of the hemagglutinin stem and head domains","volume":"19","author":"Aartse","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1016\/j.vaccine.2015.05.038","article-title":"Vaccination with soluble headless hemagglutinin protects mice from challenge with divergent influenza viruses","volume":"33","author":"Wohlbold","year":"2015","journal-title":"Vaccine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e02810-18","DOI":"10.1128\/mBio.02810-18","article-title":"Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages","volume":"10","author":"Corbett","year":"2019","journal-title":"mBio"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"eabe5449","DOI":"10.1126\/scitranslmed.abe5449","article-title":"Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates","volume":"13","author":"Qiu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17757","DOI":"10.1073\/pnas.2004783117","article-title":"Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes","volume":"117","author":"Liao","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kotey, E.N., Ampofo, W.K., Daines, R., Sadeyen, J.-R., Iqbal, M., and Quaye, O. (2021). Immune Response in Mice Immunized with Chimeric H1 Antigens. Vaccines, 9.","DOI":"10.3390\/vaccines9101182"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Corder, B.N., Bullard, B.L., DeBeauchamp, J.L., Ilyushina, N.A., Webby, R.J., and Weaver, E.A. (2019). Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice. Vaccines, 7.","DOI":"10.3390\/vaccines7040195"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"746447","DOI":"10.3389\/fimmu.2021.746447","article-title":"Mosaic Hemagglutinin-Based Whole Inactivated Virus Vaccines Induce Broad Protection Against Influenza B Virus Challenge in Mice","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00052-21","DOI":"10.1128\/mSphere.00052-21","article-title":"Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses","volume":"6","author":"Reneer","year":"2021","journal-title":"Msphere"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Huang, Y., Fran\u00e7a, M., Allen, J., Shi, H., and Ross, T. (2021). Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection. Vaccines, 9.","DOI":"10.3390\/vaccines9070793"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"707339","DOI":"10.3389\/fimmu.2021.707339","article-title":"Evaluation of Next-Generation H3 Influenza Vaccines in Ferrets Pre-Immune to Historical H3N2 Viruses","volume":"12","author":"Allen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e01243-18","DOI":"10.1128\/JVI.01243-18","article-title":"Substrate Binding by the Second Sialic Acid-Binding Site of Influenza A Virus N1 Neuraminidase Contributes to Enzymatic Activity","volume":"92","author":"Du","year":"2018","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1042\/BCJ20180764","article-title":"DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors","volume":"475","author":"Pachl","year":"2018","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Du, R., Cui, Q., and Rong, L. (2019). Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry. Viruses, 11.","DOI":"10.3390\/v11050458"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00840-19","DOI":"10.1128\/JVI.00840-19","article-title":"Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase","volume":"93","author":"Broecker","year":"2019","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Evteev, S., Nilov, D., Polenova, A., and \u0160vedas, V. (2021). Bifunctional Inhibitors of Influenza Virus Neuraminidase: Molecular Design of a Sulfonamide Linker. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313112"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/acs.bioconjchem.1c00255","article-title":"Design of Neuraminidase-Targeted Imaging and Therapeutic Agents for the Diagnosis and Treatment of Influenza Virus Infections","volume":"32","author":"Liu","year":"2021","journal-title":"Bioconjugate Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.micinf.2020.06.003","article-title":"Influenza virus glycoprotein-reactive human monoclonal antibodies","volume":"22","author":"Li","year":"2020","journal-title":"Microbes Infect."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.virol.2019.07.008","article-title":"Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus","volume":"535","author":"Kim","year":"2019","journal-title":"Virology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e02241-21","DOI":"10.1128\/mBio.02241-21","article-title":"A Novel Recombinant Influenza Virus Neuraminidase Vaccine Candidate Stabilized by a Measles Virus Phosphoprotein Tetramerization Domain Provides Robust Protection from Virus Challenge in the Mouse Model","volume":"12","author":"Strohmeier","year":"2021","journal-title":"mBio"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"JVI0075921","DOI":"10.1128\/JVI.00759-21","article-title":"Universal Influenza Virus Neuraminidase Vaccine Elicits Protective Immune Responses against Human Seasonal and Pre-pandemic Strains","volume":"95","author":"Skarlupka","year":"2021","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12929-019-0572-3","article-title":"M2e-based universal influenza vaccines: A historical overview and new approaches to development","volume":"26","author":"Mezhenskaya","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00705-017-3578-8","article-title":"An influenza A virus vaccine based on an M2e-modified alphavirus","volume":"163","author":"Krishnavajhala","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gomes, K.B., D\u2019Sa, S., Allotey-Babington, G.L., Kang, S.-M., and D\u2019Souza, M.J. (2021). Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus. Vaccines, 9.","DOI":"10.3390\/vaccines9111324"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.2174\/1389201021666201104145006","article-title":"Design, Synthesis and Primary Immunologic Evaluation of M2e-CRM197 Conjugate as a Universal Influenza Vaccine Candidate","volume":"22","author":"Xu","year":"2021","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4800","DOI":"10.1016\/j.vaccine.2021.07.032","article-title":"M2e conjugated gold nanoparticle influenza vaccine displays thermal stability at elevated temperatures and confers protection to ferrets","volume":"39","author":"Ingrole","year":"2021","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1107\/S2053230X2100635X","article-title":"Structure of an H3N2 influenza virus nucleoprotein","volume":"77","author":"Knight","year":"2021","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7774\/cevr.2019.8.1.54","article-title":"Nucleoprotein vaccine induces cross-protective cytotoxic T lymphocytes against both lineages of influenza B virus","volume":"8","author":"Lee","year":"2019","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"678483","DOI":"10.3389\/fimmu.2021.678483","article-title":"OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza","volume":"12","author":"Bouley","year":"2021","journal-title":"Frontiers in immunology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/infdis\/jiab532","article-title":"Phase 1 Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate OVX836, a Nucleoprotein-Based Influenza Vaccine: Intramuscular Results","volume":"226","author":"Withanage","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/infdis\/jiy103","article-title":"A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases","volume":"218","author":"Erbelding","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.micpath.2017.12.050","article-title":"Recombinant M2e-HA2 fusion protein induced immunity responses against intranasally administered H9N2 influenza virus","volume":"115","author":"Golchin","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11262-018-1609-5","article-title":"Chimeric protein consisting of 3M2e and HSP as a universal influenza vaccine candidate: From in silico analysis to preliminary evaluation","volume":"55","author":"Farahmand","year":"2018","journal-title":"Virus Genes"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"304","DOI":"10.4014\/jmb.2011.11029","article-title":"Influenza Chimeric Protein (3M2e-3HA2-NP) Adjuvanted with PGA\/Alum Confers Cross-Protection against Heterologous Influenza A Viruses","volume":"31","author":"Kwak","year":"2021","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e20173021","DOI":"10.1542\/peds.2017-3021","article-title":"Safety and Immunogenicity of a Recombinant Influenza Vaccine: A Randomized Trial","volume":"141","author":"Dunkle","year":"2018","journal-title":"Pediatrics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1021\/acs.bioconjchem.0c00308","article-title":"An Apoferritin\u2013Hemagglutinin Conjugate Vaccine with Encapsulated Nucleoprotein Antigen Peptide from Influenza Virus Confers Enhanced Cross Protection","volume":"31","author":"Wei","year":"2020","journal-title":"Bioconjugate Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"102479","DOI":"10.1016\/j.nano.2021.102479","article-title":"Influenza NP core and HA or M2e shell double-layered protein nanoparticles induce broad protection against divergent influenza A viruses","volume":"40","author":"Ma","year":"2021","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1039\/D1NR08460G","article-title":"A self-assembling nanoparticle vaccine targeting the conserved epitope of influenza virus hemagglutinin stem elicits a cross-protective immune response","volume":"14","author":"Qiao","year":"2022","journal-title":"Nanoscale"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-021-03365-x","article-title":"Quadrivalent influenza nanoparticle vaccines induce broad protection","volume":"592","author":"Ellis","year":"2021","journal-title":"Nature"},{"key":"ref_81","first-page":"e62226","article-title":"Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform","volume":"168","author":"Ghosh","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.2147\/IJN.S198353","article-title":"Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: State of the art, emerging technologies, and perspectives","volume":"14","author":"Mukherjee","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104885","DOI":"10.1016\/j.micpath.2021.104885","article-title":"Preparation and evaluation of virus-like particle vaccine against H3N8 subtype equine influenza","volume":"157","author":"Zhang","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"109306","DOI":"10.1016\/j.vetmic.2021.109306","article-title":"Baculovirus-derived influenza virus-like particle confers complete protection against lethal H7N9 avian influenza virus challenge in chickens and mice","volume":"264","author":"Hu","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"109106","DOI":"10.1016\/j.vetmic.2021.109106","article-title":"H7N9 influenza virus-like particle based on BEVS protects chickens from lethal challenge with highly pathogenic H7N9 avian influenza virus","volume":"258","author":"Li","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"16643","DOI":"10.1002\/jcp.28339","article-title":"Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model","volume":"234","author":"Keshavarz","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1002\/jssc.201901215","article-title":"Separation of influenza virus-like particles from baculovirus by polymer-grafted anion exchanger","volume":"43","author":"Reiter","year":"2020","journal-title":"J. Sep. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1016\/j.vaccine.2020.07.015","article-title":"A biomimetic VLP influenza vaccine with interior NP\/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy","volume":"38","author":"Wei","year":"2020","journal-title":"Vaccine"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Pushko, P., and Tretyakova, I. (2020). Influenza Virus Like Particles (VLPs): Opportunities for H7N9 Vaccine Development. Viruses, 12.","DOI":"10.3390\/v12050518"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1080\/14760584.2019.1704262","article-title":"Advances in influenza virus-like particles bioprocesses","volume":"18","author":"Durous","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"107757","DOI":"10.1016\/j.bej.2020.107757","article-title":"Production of influenza virus-like particles using recombinant insect cells","volume":"163","author":"Matsuda","year":"2020","journal-title":"Biochem. Eng. J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1016\/j.vaccine.2020.09.062","article-title":"Protective efficacy of a polyvalent influenza A DNA vaccine against both homologous (H1N1pdm09) and heterologous (H5N1) challenge in the ferret model","volume":"39","author":"Guilfoyle","year":"2021","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/22221751.2018.1558962","article-title":"Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine","volume":"8","author":"Yao","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/JLB.6A1021-535R","article-title":"Hemagglutinin-based DNA vaccines containing trimeric self-assembling nanoparticles confer protection against influenza","volume":"112","author":"Qiao","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.3389\/fimmu.2018.01568","article-title":"A Review of DNA Vaccines Against Influenza","volume":"9","author":"Lee","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"747032","DOI":"10.3389\/fimmu.2021.747032","article-title":"Pandemic Preparedness Against Influenza: DNA Vaccine for Rapid Relief","volume":"12","author":"Andersen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41541-020-0159-8","article-title":"The promise of mRNA vaccines: A biotech and industrial perspective","volume":"5","author":"Jackson","year":"2020","journal-title":"npj Vaccines"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhuang, X., Qi, Y., Wang, M., Yu, N., Nan, F., Zhang, H., Tian, M., Li, C., Lu, H., and Jin, N. (2020). mRNA Vaccines Encoding the HA Protein of Influenza A H1N1 Virus Delivered by Cationic Lipid Nanoparticles Induce Protective Immune Responses in Mice. Vaccines, 8.","DOI":"10.3390\/vaccines8010123"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.ymthe.2020.04.018","article-title":"A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice","volume":"28","author":"Freyn","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41541-021-00420-6","article-title":"Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza","volume":"6","author":"Chivukula","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"001765","DOI":"10.1099\/jgv.0.001765","article-title":"Message in a bottle: mRNA vaccination for influenza","volume":"103","author":"Shartouny","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1080\/14760584.2022.2053678","article-title":"Thermostable vaccines: An innovative concept in vaccine development","volume":"21","author":"Kumar","year":"2022","journal-title":"Expert Rev. Vaccines"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1016\/j.vaccine.2021.03.038","article-title":"mRNA vaccines manufacturing: Challenges and bottlenecks","volume":"39","author":"Rosa","year":"2021","journal-title":"Vaccine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.copbio.2021.09.016","article-title":"Principles for designing an optimal mRNA lipid nanoparticle vaccine","volume":"73","author":"Kon","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s10529-020-02822-3","article-title":"An approach to the influenza chimeric subunit vaccine (3M2e-HA2-NP) provides efficient protection against lethal virus challenge","volume":"42","author":"Saleh","year":"2020","journal-title":"Biotechnol. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Jafari, D., Malih, S., Gomari, M.M., Safari, M., Jafari, R., and Farajollahi, M.M. (2020). Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: A bioinformatics study. BMC Cell Biol., 21.","DOI":"10.1186\/s12860-020-00334-6"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"152053","DOI":"10.1016\/j.imbio.2021.152053","article-title":"Immunoinformatics approach for a novel multi-epitope subunit vaccine design against various subtypes of Influenza A virus","volume":"226","author":"Sharma","year":"2021","journal-title":"Immunobiology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.actbio.2021.06.023","article-title":"From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases","volume":"131","author":"Pilkington","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_110","first-page":"311","article-title":"Tailoring mRNA Vaccine to Balance Innate\/Adaptive Immune Response","volume":"26","author":"Lacroix","year":"2019","journal-title":"Trends Mol. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:48:49Z","timestamp":1760147329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/1\/116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["v15010116"],"URL":"https:\/\/doi.org\/10.3390\/v15010116","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}