{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:30:49Z","timestamp":1790951449342,"version":"4.1.0"},"reference-count":123,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.<\/jats:p>","DOI":"10.1111\/irv.13276","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T19:00:50Z","timestamp":1711047650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines"],"prefix":"10.1111","volume":"18","author":[{"given":"Caryn Myn Li","family":"Lim","sequence":"first","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine &amp; Health Sciences Monash University Malaysia  Bandar Sunway Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamil Vaani","family":"Komarasamy","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine &amp; Health Sciences Monash University Malaysia  Bandar Sunway Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-3376","authenticated-orcid":false,"given":"Nur Amelia Azreen Binti","family":"Adnan","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine &amp; Health Sciences Monash University Malaysia  Bandar Sunway Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammu Kutty","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine &amp; Health Sciences Monash University Malaysia  Bandar Sunway Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod R. M. T.","family":"Balasubramaniam","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine &amp; Health Sciences Monash University Malaysia  Bandar Sunway Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30129-0"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0002-y"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-06"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2005.09.002"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12091033"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.407"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030151"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0143-6"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0340-z"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1462639"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2017.0141"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1584801"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines7040169"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy103"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12887"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1714916"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.563850"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.069542-0"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01875-17"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.005"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1201-1306"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00743"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222213"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01526-18"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy711"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-120617-041310"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1805713115"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02725-4"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201901176"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310612"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-020-00762-4"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.09.020"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.243"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/amp2.10060"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00283-5"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038778"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40175-8"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-018-0025-9"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.03.007"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2020.1857162"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad0522"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204839"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111745"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2018.11.005"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00728-5"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-019-0111-y"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1123805"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2018.1541408"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-021-00676-9"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03365-x"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01660-8"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00420-6"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.04.018"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0271"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2017.1355245"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161193"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-021-00176-7"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.074"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30556-0"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1118-7"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30393-7"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2004783117"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00333-19"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe5449"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00018\u201010"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3927"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7263"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-019-0126-4"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05482-0"},{"key":"e_1_2_16_73_1","volume-title":"Clinical Trial of mRNA Universal Influenza Vaccine Candidate Begins","author":"Deatrick E.","year":"2023"},{"key":"e_1_2_16_74_1","first-page":"195","article-title":"Hemagglutinin Consensus\u2010Based Prophylactic Approaches to Overcome Influenza Virus Diversity","volume":"55","author":"Sautto G. A.","year":"2019","journal-title":"Veterinaria Italiana"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01581-17"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03152-15"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900379"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01526-20"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0305-x"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay0678"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01679\u201020"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03313-14"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.08.015"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00759-21"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02315\u201020"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv313"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02332\u201017"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.10143"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8030409"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-018-0093-1"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu539"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz003"},{"key":"e_1_2_16_93_1","first-page":"162","article-title":"Plant\u2010Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin","volume":"9","author":"Blokhina E. A.","year":"2020","journal-title":"Plants (Basel, Switzerland)"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0572-3"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025607119"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.04.073"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83704-0"},{"key":"e_1_2_16_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.05.041"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00072-2"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27662"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq015"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.08.031"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-011-9632-5"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.03.023"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.1086\/500247"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2017.11.018"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0696-0"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc9937"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2436"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01479"},{"key":"e_1_2_16_111_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028845"},{"key":"e_1_2_16_112_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1619406"},{"key":"e_1_2_16_113_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2019.1604671"},{"key":"e_1_2_16_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.07.007"},{"key":"e_1_2_16_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110482"},{"key":"e_1_2_16_116_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-020-0626-6"},{"key":"e_1_2_16_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.06.016"},{"key":"e_1_2_16_118_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy696"},{"key":"e_1_2_16_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0056-x"},{"key":"e_1_2_16_120_1","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12706"},{"key":"e_1_2_16_121_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008583"},{"key":"e_1_2_16_122_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0937-x"},{"key":"e_1_2_16_123_1","doi-asserted-by":"publisher","DOI":"10.1080\/08830185.2019.1685990"},{"key":"e_1_2_16_124_1","doi-asserted-by":"crossref","unstructured":"G.PawelecandJ.McElhaney \u201cRecent Advances in Influenza Vaccines [version 1; peer review: 2 approved] \u201dF1000Research9 (2020):305.","DOI":"10.12688\/f1000research.22611.1"}],"container-title":["Influenza and Other Respiratory Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/irv.13276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T21:44:35Z","timestamp":1711403075000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/irv.13276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":123,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/irv.13276"],"URL":"https:\/\/doi.org\/10.1111\/irv.13276","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/IRV.13276\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/IRV.13276\/v3\/response1","asserted-by":"object"}]},"ISSN":["1750-2640","1750-2659"],"issn-type":[{"value":"1750-2640","type":"print"},{"value":"1750-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13276"}}