{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:37:01Z","timestamp":1792211821886,"version":"4.4.0"},"reference-count":140,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indian Council of Medical Research","award":["IIRP-2023-3052"],"award-info":[{"award-number":["IIRP-2023-3052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Influenza is a serious and global health issue, and it is a major cause of morbidity, fatality, and economic loss every year. Seasonal vaccines exist but are not very effective due to strain mismatches, delays in production, and antigenic drift. This comprehensive overview discusses the current situation of influenza vaccination, including the numerous types of vaccines\u2014inactivated, live attenuated, and recombinant vaccines\u2014and their effectiveness, efficacy, and associated challenges. It highlights the effects of the COVID-19 pandemic on the trends of influenza vaccination and the level to which innovation should be practiced. In the future universal influenza vaccines will be developed that target conserved viral antigens to provide long-term protection to people. In the meantime, novel vaccine delivery platforms, such as mRNA technology, virus-like particle (VLP), and nanoparticle-based systems, and less cumbersome and invasive administration routes, as well as immune responses are also under development to increase access and production capacity. Collectively, these innovations have the potential to not only reduce the global influenza epidemic but also to change the way influenza is prevented and prepare the world for a pandemic.<\/jats:p>","DOI":"10.3390\/vaccines13090890","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T13:47:49Z","timestamp":1755870469000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Influenza Virus: Global Health Impact, Strategies, Challenges, Role of Nanotechnolgy in Influenza Vaccine Development"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-0751","authenticated-orcid":false,"given":"Shabi","family":"Parvez","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, IFTM University, Moradabad 244102, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5525-0543","authenticated-orcid":false,"given":"Anushree","family":"Pathrathota","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3780-4689","authenticated-orcid":false,"given":"Arjun L.","family":"Uppar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, BLDEA\u2019s Shri Sanganabasava Mahaswamiji College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-6006","authenticated-orcid":false,"given":"Ganesh","family":"Yadagiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3466-0616","authenticated-orcid":false,"given":"Shyam Lal","family":"Mudavath","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad, Prof. C.R. Rao Road, Gachibowli, Hyderabad 500046, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","first-page":"751","article-title":"Influenza: Diagnosis and Treatment","volume":"100","author":"Gaitonde","year":"2019","journal-title":"Am. Fam. Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S1473-3099(02)00366-3","article-title":"Influenza\u2014WHO cares","volume":"2","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1016\/j.vaccine.2021.05.011","article-title":"Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research","volume":"39","author":"Ferdinands","year":"2021","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"To, J., and Torres, J. (2019). Viroporins in the Influenza Virus. Cells, 8.","DOI":"10.3390\/cells8070654"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.virusres.2011.09.022","article-title":"Immune responses to influenza virus infection","volume":"162","author":"Kreijtz","year":"2011","journal-title":"Virus Res."},{"key":"ref_6","unstructured":"Influenza (Seasonal). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"ref_7","unstructured":"Pandemic Influenza\u2014Overview|Occupational Safety and Health Administration, Available online: https:\/\/www.osha.gov\/pandemic-influenza."},{"key":"ref_8","unstructured":"World Health Organization Emergency Cycle\u2014Pandemic Influenza\u2014A Threat That All Countries Need to Prepare for. Available online: https:\/\/www.who.int\/europe\/emergencies\/emergency-cycle\/prepare\/pandemic-influenza."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ashraf, M.A., Raza, M.A., Amjad, M.N., ud Din, G., Yue, L., Shen, B., Chen, L., Dong, W., Xu, H., and Hu, Y. (2024). A comprehensive review of influenza B virus, its biological and clinical aspects. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1467029"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Emerging Influenza D Virus Threat: What We Know so Far!. Available online: https:\/\/www.mdpi.com\/2077-0383\/8\/2\/192.","DOI":"10.3390\/jcm8020192"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, B., Cao, B., Wang, C., Han, B., Sun, T., Miao, Y., Lu, Q., and Cui, F. (2022). Immunogenicity and Safety of Childhood Combination Vaccines: A Systematic Review and Meta-Analysis. Vaccines, 10.","DOI":"10.3390\/vaccines10030472"},{"key":"ref_12","unstructured":"Vaccines. Available online: https:\/\/www.who.int\/teams\/global-influenza-programme\/vaccines."},{"key":"ref_13","unstructured":"Influenza Vaccination for Elderly, Vulnerable and High-Risk Subjects: A Narrative Review and Expert Opinion\u2014PMC, Available online: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC11039544\/."},{"key":"ref_14","unstructured":"CDC H5 Bird Flu: Current Situation, Available online: https:\/\/www.cdc.gov\/bird-flu\/situation-summary\/index.html."},{"key":"ref_15","unstructured":"CDC CDC Confirms First Severe Case of H5N1 Bird Flu in the United States, Available online: https:\/\/www.cdc.gov\/media\/releases\/2024\/m1218-h5n1-flu.html."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cordeiro, A.S., Patil-Sen, Y., Shivkumar, M., Patel, R., Khedr, A., and Elsawy, M.A. (2021). Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122091"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104125","DOI":"10.1016\/j.drudis.2024.104125","article-title":"Deciphering immune responses: A comparative analysis of influenza vaccination platforms","volume":"29","author":"Jones","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.antiviral.2011.07.013","article-title":"A potential role for monoclonal antibodies in prophylactic and therapeutic treatment of influenza","volume":"92","author":"Mancini","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_19","unstructured":"Orenstein, W.A., Offit, P.A., Edwards, K.M., and Plotkin, S.A. (2022). Plotkin\u2019s Vaccines, E-Book, Elsevier Health Sciences."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41577-019-0143-6","article-title":"The human antibody response to influenza A virus infection and vaccination","volume":"19","author":"Krammer","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4161\/hv.22908","article-title":"Correlates of protection to influenza virus, where do we go from here?","volume":"9","author":"Cox","year":"2013","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10435","DOI":"10.1128\/JVI.01715-13","article-title":"Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses","volume":"87","author":"Margine","year":"2013","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gao, R., Sheng, Z., Sreenivasan, C.C., Wang, D., and Li, F. (2020). Influenza A Virus Antibodies with Antibody-Dependent Cellular Cytotoxicity Function. Viruses, 12.","DOI":"10.3390\/v12030276"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zarnitsyna, V.I., Ellebedy, A.H., Davis, C., Jacob, J., Ahmed, R., and Antia, R. (2015). Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza. Philos. Trans. R. Soc. B Biol. Sci., 370.","DOI":"10.1098\/rstb.2014.0248"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2018.03.030","article-title":"Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies","volume":"173","author":"Chen","year":"2018","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.virol.2017.06.006","article-title":"Neuraminidase-based recombinant virus-like particles protect against lethal avian influenza A(H5N1) virus infection in ferrets","volume":"509","author":"Smith","year":"2017","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJM198307073090103","article-title":"Cytotoxic T-Cell Immunity to Influenza","volume":"309","author":"McMichael","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/icb.2009.16","article-title":"Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes","volume":"87","author":"Brown","year":"2009","journal-title":"Immunol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Brown, D.M., Lampe, A.T., and Workman, A.M. (2016). The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00093"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0167-5699(92)90083-J","article-title":"Induction of TH1 and TH2 responses: A key role for the \u201cnatural\u201d immune response?","volume":"13","author":"Romagnani","year":"1992","journal-title":"Immunol. Today"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101495","DOI":"10.1016\/j.trim.2021.101495","article-title":"T helper type (Th1\/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses","volume":"70","author":"Molavi","year":"2022","journal-title":"Transpl. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jcv.2019.08.009","article-title":"Influenza virus-specific CD4+ and CD8+ T cell-mediated immunity induced by infection and vaccination","volume":"119","author":"Jansen","year":"2019","journal-title":"J. Clin. Virol. Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5893","DOI":"10.1016\/j.vaccine.2012.04.109","article-title":"Mucosal IgA responses in influenza virus infections; thoughts for vaccine design","volume":"30","author":"Ainai","year":"2012","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41385-021-00461-z","article-title":"Tissue resident memory T cells in the respiratory tract","volume":"15","author":"Zheng","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/vaccines3020373","article-title":"Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines","volume":"3","author":"Sridhar","year":"2015","journal-title":"Vaccines"},{"key":"ref_37","unstructured":"Types of Seasonal Influenza Vaccine. Available online: https:\/\/www.who.int\/europe\/news-room\/fact-sheets\/item\/types-of-seasonal-influenza-vaccine."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/irv.12087","article-title":"Vaccination of healthcare workers to protect patients at increased risk of acute respiratory disease: Summary of a systematic review","volume":"7","author":"Dolan","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_39","unstructured":"The Human Antibody Response to Influenza a Virus Infection and Vaccination | Nature Reviews Immunology. Available online: https:\/\/www.nature.com\/articles\/s41577-019-0143-6."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7201a1","article-title":"Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations\u2014United States, 2023","volume":"72","author":"Conners","year":"2023","journal-title":"MMWR Recomm. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4161\/hv.8.1.17623","article-title":"The Rationale for Quadrivalent Influenza Vaccines","volume":"8","author":"Ambrose","year":"2012","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Folegatti, P.M., Pepin, S., Tabar, C., Fries, K., Talanova, O., See, S., Essink, B., Bertoch, T., Drazan, D., and Natalini Mart\u00ednez, S. (2025). Comparative assessment of immunogenicity and safety of recombinant influenza vaccine in children, adolescents, and adults: Results from a phase 3, immunobridging, open-label, non-randomised study. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(25)00153-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1093\/infdis\/jiy711","article-title":"Universal Influenza Virus Vaccines That Target the Conserved Hemagglutinin Stalk and Conserved Sites in the Head Domain","volume":"219","author":"Krammer","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17","DOI":"10.32607\/20758251-2012-4-4-17-27","article-title":"Recombinant Influenza Vaccines","volume":"4","author":"Sedova","year":"2012","journal-title":"Acta Naturae"},{"key":"ref_45","unstructured":"Novavax (2023). A Phase 3, Randomized, Observer-Blinded, Active-Controlled Trial to Evaluate Immunogenicity; Safety of a Recombinant Quadrivalent Nanoparticle Influenza Vaccine (Quad-NIV) with Matrix-M1TM Adjuvant Against Fluzone\u00ae Quadrivalent in Clinically Stable Adults \u2265 65 Years of Age, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04120194."},{"key":"ref_46","unstructured":"National Institute of Allergy and Infectious Diseases (NIAID) (2025). Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of the Safety and Immunogenicity of BPL-1357, A BPL-Inactivated, Whole-Virus, Universal Influenza Vaccine, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05027932."},{"key":"ref_47","unstructured":"Radboud University Medical Center First-in-Human Trial of the Coronavirus Virus-like Particle Subunit Vaccine ABNCoV2 in SARS-CoV-2-Na\u00efve Adult Volunteers in Good Health. Available online: https:\/\/onderzoekmetmensen.nl\/en\/node\/50898\/pdf."},{"key":"ref_48","unstructured":"BioNTech SE (2023). A PHASE 1\/2\/3, Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of SARS-COV-2 RNA Vaccine Candidates Against COVID-19 in Healthy Individuals, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04368728."},{"key":"ref_49","unstructured":"ModernaTX, Inc (2023). A Phase 1\/2, Randomized, Stratified, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults 18 Years and Older, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04956575."},{"key":"ref_50","unstructured":"National Institute of Allergy and Infectious Diseases (NIAID) (2022). VRC 321: A Phase I Open-Label Clinical Trial to Evaluate Dose, Safety, Tolerability, and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine, VRCFLUNPF099-00-VP, in Healthy Adults, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03814720."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.1016\/j.vaccine.2009.06.014","article-title":"Vaxfectin\u00ae, a cationic lipid-based adjuvant for protein-based influenza vaccines","volume":"27","author":"Hartikka","year":"2009","journal-title":"Vaccine"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Trombetta, C.M., Kistner, O., Montomoli, E., Viviani, S., and Marchi, S. (2022). Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines. Vaccines, 10.","DOI":"10.3390\/vaccines10050714"},{"key":"ref_53","unstructured":"Evaluation of Influenza Vaccine Effectiveness\u2014A Guide to the Design and Interpretation of Observational Studies. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241512121."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1016\/j.vaccine.2020.06.021","article-title":"The impact of candidate influenza virus and egg-based manufacture on vaccine effectiveness: Literature review and expert consensus","volume":"38","author":"Rajaram","year":"2020","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S2213-2600(22)00266-1","article-title":"Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis","volume":"11","author":"Robinson","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_56","unstructured":"CDC Benefits of the Flu Vaccine, Available online: https:\/\/www.cdc.gov\/flu-vaccines-work\/benefits\/index.html."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa1608862","article-title":"Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older","volume":"376","author":"Dunkle","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_58","unstructured":"CDC Flu Vaccine Effectiveness (VE) Data for 2022\u20132023, Available online: https:\/\/www.cdc.gov\/flu-vaccines-work\/php\/effectiveness-studies\/2022-2023.html."},{"key":"ref_59","unstructured":"CDC U.S. Flu Vaccine Effectiveness (VE) Data for 2021\u20132022, Available online: https:\/\/www.cdc.gov\/flu-vaccines-work\/php\/effectiveness-studies\/2021-2022.html."},{"key":"ref_60","unstructured":"News Release. Available online: https:\/\/feeds.issuerdirect.com\/news-release.html?newsid=4899326521164266&symbol=MRNA."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.biochem.69.1.531","article-title":"Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin","volume":"69","author":"Skehel","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.vaccine.2019.11.041","article-title":"Quantification of the total neuraminidase content of recent commercially-available influenza vaccines: Introducing a neuraminidase titration reagent","volume":"38","author":"Gao","year":"2020","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev-virology-010320-044746","article-title":"Challenges of Making Effective Influenza Vaccines","volume":"7","author":"Gouma","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1056\/NEJMp038238","article-title":"Influenza vaccine--outmaneuvering antigenic shift and drift","volume":"350","author":"Treanor","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_65","unstructured":"Influenza | Nature Reviews Disease Primers. Available online: https:\/\/www.nature.com\/articles\/s41572-018-0002-y."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/irv.12570","article-title":"65 years of influenza surveillance by a World Health Organization-coordinated global network","volume":"12","author":"Ziegler","year":"2018","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.vaccine.2009.11.043","article-title":"Epidemiological, antigenic and genetic characteristics of seasonal influenza A(H1N1), A(H3N2) and B influenza viruses: Basis for the WHO recommendation on the composition of influenza vaccines for use in the 2009\u20132010 northern hemisphere season","volume":"28","author":"Barr","year":"2010","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mohan, H., Narang, J., Pundir, S., and Pundir, C.S. (2021). A changing trend in diagnostic methods of Influenza A (H3N2) virus in human: A review. 3 Biotech, 11.","DOI":"10.1007\/s13205-021-02642-w"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1126\/science.1097211","article-title":"Mapping the antigenic and genetic evolution of influenza virus","volume":"305","author":"Smith","year":"2004","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coviro.2016.12.004","article-title":"Immune history and influenza virus susceptibility","volume":"22","author":"Cobey","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1016\/S0264-410X(03)00071-9","article-title":"The annual production cycle for influenza vaccine","volume":"21","author":"Gerdil","year":"2003","journal-title":"Vaccine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105505","DOI":"10.1016\/j.antiviral.2022.105505","article-title":"The race toward a universal influenza vaccine: Front runners and the future directions","volume":"210","author":"Hu","year":"2023","journal-title":"Antiviral Res."},{"key":"ref_73","unstructured":"Despite Global Influenza Vaccine Production Remaining Steady, Production and Distribution Challenges Remain. Available online: https:\/\/www.who.int\/news\/item\/25-03-2025-despite-global-influenza-vaccine-production-remaining-steady--production-and-distribution-challenges-remain."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00705-024-06210-4","article-title":"Next-generation vaccines for influenza B virus: Advancements and challenges","volume":"170","author":"Ashraf","year":"2025","journal-title":"Arch. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2426284","DOI":"10.1080\/21645515.2024.2426284","article-title":"Impact of COVID-19 pandemic on influenza vaccination rate among health care workers","volume":"20","author":"Alshagrawi","year":"2024","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2477954","DOI":"10.1080\/21645515.2025.2477954","article-title":"Impact of COVID-19 pandemic on influenza vaccination rates among healthcare workers and the general population in Saudi Arabia: A meta-analysis","volume":"21","author":"Alshagrawi","year":"2025","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_77","unstructured":"Influenza Vaccination During the COVID-19 Pandemic IFPMA. Available online: https:\/\/www.ifpma.org\/wp-content\/uploads\/2023\/01\/i2023_IFPMA_HPP_Influenza_vaccination_during_COVID-19_pandemic.pdf."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s40121-024-01079-x","article-title":"The Impact of Vaccination on COVID-19, Influenza, and Respiratory Syncytial Virus-Related Outcomes: A Narrative Review","volume":"14","author":"Debbag","year":"2025","journal-title":"Infect. Dis. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Awate, S., Babiuk, L.A., and Mutwiri, G. (2013). Mechanisms of Action of Adjuvants. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00114"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1773-2247(10)50044-3","article-title":"From single-dose vaccine delivery systems to nanovaccines","volume":"20","author":"Vicente","year":"2010","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.vaccine.2013.11.069","article-title":"Nanoparticle vaccines","volume":"32","author":"Zhao","year":"2014","journal-title":"Vaccine"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s12038-009-0114-3","article-title":"Nanovaccines: Recent developments in vaccination","volume":"34","author":"Nandedkar","year":"2009","journal-title":"J. Biosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"eabp8964","DOI":"10.1126\/science.abp8964","article-title":"The extracellular matrix and the immune system: A mutually dependent relationship","volume":"379","author":"Sutherland","year":"2023","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Abusalah, M.A.H., Chopra, H., Sharma, A., Mustafa, S.A., Choudhary, O.P., Sharma, M., Dhawan, M., Khosla, R., and Loshali, A. (2023). Nanovaccines: A game changing approach in the fight against infectious diseases. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115597"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Pati, R., Shevtsov, M., and Sonawane, A. (2018). Nanoparticle Vaccines Against Infectious Diseases. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02224"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"122331","DOI":"10.1016\/j.lfs.2023.122331","article-title":"Vaccine development: Current trends and technologies","volume":"336","author":"Poria","year":"2024","journal-title":"Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ymeth.2006.07.018","article-title":"Virus-like particles: Passport to immune recognition","volume":"40","author":"Grgacic","year":"2006","journal-title":"Methods San Diego Calif"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/1568005033481213","article-title":"Particle-based vaccines for HIV-1 infection","volume":"3","author":"Young","year":"2003","journal-title":"Curr. Drug Targets Infect. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.tibtech.2013.09.002","article-title":"Virus-like particle-based human vaccines: Quality assessment based on structural and functional properties","volume":"31","author":"Zhao","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1016\/j.vaccine.2007.01.106","article-title":"Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin","volume":"25","author":"Bright","year":"2007","journal-title":"Vaccine"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1016\/j.vaccine.2011.05.001","article-title":"Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2.HA1 SI)","volume":"29","author":"Taylor","year":"2011","journal-title":"Vaccine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"11813","DOI":"10.1128\/JVI.01076-08","article-title":"Incorporation of membrane-anchored flagellin into influenza virus-like particles enhances the breadth of immune responses","volume":"82","author":"Wang","year":"2008","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.addr.2018.06.025","article-title":"Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases","volume":"145","author":"Tao","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1021\/nn4006544","article-title":"Biomimetic antigenic nanoparticles elicit controlled protective immune response to influenza","volume":"7","author":"Patterson","year":"2013","journal-title":"ACS Nano"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1094\/PHYTO.2004.94.11.1245","article-title":"Taxonomy of the genus bacillus and related genera: The aerobic endospore-forming bacteria","volume":"94","author":"Fritze","year":"2004","journal-title":"Phytopathology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrmicro2921","article-title":"The Bacillus subtilis endospore: Assembly and functions of the multilayered coat","volume":"11","author":"McKenney","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1016\/j.vaccine.2004.05.001","article-title":"Oral priming of mice by recombinant spores of Bacillus subtilis","volume":"22","author":"Ciabattini","year":"2004","journal-title":"Vaccine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1128\/IAI.71.5.2810-2818.2003","article-title":"Bacterial spores as vaccine vehicles","volume":"71","author":"Duc","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.4161\/hv.36122","article-title":"Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine","volume":"10","author":"Zhao","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1016\/j.vaccine.2012.03.016","article-title":"Killed Bacillus subtilis spores as a mucosal adjuvant for an H5N1 vaccine","volume":"30","author":"Song","year":"2012","journal-title":"Vaccine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.carbpol.2015.05.079","article-title":"Structure-function relationships of immunostimulatory polysaccharides: A review","volume":"132","author":"Ferreira","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.coi.2010.04.004","article-title":"New adjuvants for human vaccines","volume":"22","author":"Mbow","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"8549","DOI":"10.1016\/j.vaccine.2011.09.029","article-title":"Preparation and immunological effectiveness of a swine influenza DNA vaccine encapsulated in chitosan nanoparticles","volume":"29","author":"Zhao","year":"2011","journal-title":"Vaccine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1007\/s11605-023-05654-4","article-title":"Gut Barrier Dysfunction and Bacterial Lipopolysaccharides in Colorectal Cancer","volume":"27","author":"Li","year":"2023","journal-title":"J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Ahmed, A.A.Q., Besio, R., Xiao, L., and Forlino, A. (2023). Outer Membrane Vesicles (OMVs) as Biomedical Tools and Their Relevance as Immune-Modulating Agents against H. pylori Infections: Current Status and Future Prospects. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108542"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e72923","DOI":"10.7554\/eLife.72923","article-title":"IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity","volume":"12","author":"Schick","year":"2023","journal-title":"eLife"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Shehata, M.M., Mostafa, A., Teubner, L., Mahmoud, S.H., Kandeil, A., Elshesheny, R., Boubak, T.A., Frantz, R., Pietra, L.L., and Pleschka, S. (2019). Bacterial Outer Membrane Vesicles (OMVs)-Based Dual Vaccine for Influenza A H1N1 Virus and MERS-CoV. Vaccines, 7.","DOI":"10.3390\/vaccines7020046"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Cai, X., Yao, J., Guo, H., Yin, L., Leung, W., and Xu, C. (2020). Role of Extracellular Vesicles in Influenza Virus Infection. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00366"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.procbio.2023.02.028","article-title":"Extracellular vesicles in vaccine development and therapeutic approaches for viral diseases","volume":"128","author":"Pordanjani","year":"2023","journal-title":"Process Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Sabanovic, B., Piva, F., Cecati, M., and Giulietti, M. (2021). Promising Extracellular Vesicle-Based Vaccines against Viruses, Including SARS-CoV-2. Biology, 10.","DOI":"10.3390\/biology10020094"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Santos, P., and Almeida, F. (2021). Exosome-Based Vaccines: History, Current State, and Clinical Trials. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.711565"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"309602","DOI":"10.1155\/2015\/309602","article-title":"Therapeutic Potential of Inorganic Nanoparticles for the Delivery of Monoclonal Antibodies","volume":"2015","author":"Turner","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1039\/C1CS15237H","article-title":"The golden age: Gold nanoparticles for biomedicine","volume":"41","author":"Dreaden","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.nano.2018.03.007","article-title":"Gold nanoparticles conjugating recombinant influenza hemagglutinin trimers and flagellin enhanced mucosal cellular immunity","volume":"14","author":"Wang","year":"2018","journal-title":"Nanomedicine Nanotechnol. Biol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1016\/j.vaccine.2015.03.063","article-title":"M2e-immobilized gold nanoparticles as influenza A vaccine: Role of soluble M2e and longevity of protection","volume":"33","author":"Tao","year":"2015","journal-title":"Vaccine"},{"key":"ref_116","first-page":"2786","article-title":"Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant","volume":"14","author":"Neto","year":"2018","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.nano.2015.11.020","article-title":"Superparamagnetic iron oxide nanoparticle uptake alters M2 macrophage phenotype, iron metabolism, migration and invasion","volume":"12","author":"Rojas","year":"2016","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1039\/c3nr00357d","article-title":"Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery","volume":"5","author":"Mody","year":"2013","journal-title":"Nanoscale"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"7829","DOI":"10.1016\/j.vaccine.2010.09.087","article-title":"Immunological parameters related to the adjuvant effect of the ordered mesoporous silica SBA-15","volume":"28","author":"Carvalho","year":"2010","journal-title":"Vaccine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"16982","DOI":"10.1021\/acsnano.1c04996","article-title":"Lipid Nanoparticles\u2500From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement","volume":"15","author":"Tenchov","year":"2021","journal-title":"ACS Nano"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41565-020-0739-9","article-title":"Advances in nanomaterial vaccine strategies to address infectious diseases impacting global health","volume":"16","author":"Fries","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1586\/erv.11.126","article-title":"The long-term potential of biodegradable poly(lactide-co-glycolide) microparticles as the next-generation vaccine adjuvant","volume":"10","author":"Jain","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/mp100255c","article-title":"Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine","volume":"8","author":"Thomas","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ejpb.2013.06.017","article-title":"Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: Effect of mucoadhesive coating on antigen uptake and immune adjuvant activity","volume":"85","author":"Pawar","year":"2013","journal-title":"Eur. J. Pharm. Biopharm. Off. J. Arbeitsgem. Pharm. Verfahrenstech. EV"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0169-409X(02)00228-4","article-title":"Biodegradable nanoparticles for drug and gene delivery to cells and tissue","volume":"55","author":"Panyam","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1208\/s12248-023-00844-z","article-title":"Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles","volume":"25","author":"Kim","year":"2023","journal-title":"AAPS J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1021\/acsinfecdis.8b00206","article-title":"A perspective of nanoparticle universal influenza vaccines","volume":"4","author":"Deng","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Jitoboam, K., Phaonakrop, N., Libsittikul, S., Thepparit, C., Roytrakul, S., and Smith, D.R. (2016). Actin Interacts with Dengue Virus 2 and 4 Envelope Proteins. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151951"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.vaccine.2012.12.064","article-title":"An investigation of three injections techniques in reducing local injection pain with a human papillomavirus vaccine: A randomized trial","volume":"31","author":"Poole","year":"2013","journal-title":"Vaccine"},{"key":"ref_130","unstructured":"Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection|Nature Medicine. Available online: https:\/\/www.nature.com\/articles\/nm.3927."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.ijpharm.2018.05.052","article-title":"Pentaglycine lipid derivates\u2014rp-HPLC analytics for bioorthogonal anchor molecules in targeted, multiple-composite liposomal drug delivery systems","volume":"547","author":"Schiller","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1016\/j.vaccine.2018.05.072","article-title":"Protective immune response against Toxoplasma gondii elicited by a novel yeast-based vaccine with microneme protein 16","volume":"36","author":"Wang","year":"2018","journal-title":"Vaccine"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.bbamem.2010.04.015","article-title":"Influenza M2 proton channels","volume":"1808","author":"Pielak","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"13029","DOI":"10.1128\/JVI.01430-14","article-title":"Stepwise priming by acidic pH and a high K+ concentration is required for efficient uncoating of influenza A virus cores after penetration","volume":"88","author":"Stauffer","year":"2014","journal-title":"J. Virol."},{"key":"ref_135","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_136","doi-asserted-by":"crossref","unstructured":"Nguyen, Q.-T., and Choi, Y.-K. (2021). Targeting Antigens for Universal Influenza Vaccine Development. Viruses, 13.","DOI":"10.3390\/v13060973"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Wang, W.-C., Sayedahmed, E.E., Sambhara, S., and Mittal, S.K. (2022). Progress towards the Development of a Universal Influenza Vaccine. Viruses, 14.","DOI":"10.3390\/v14081684"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nm.3927","article-title":"Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection","volume":"21","author":"Yassine","year":"2015","journal-title":"Nat. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41541-025-01145-6","article-title":"Comparing Moderna\u2019s mRNA-1083 and Pfizer\u2019s dual-target mRNA vaccines for influenza and COVID-19","volume":"10","author":"Akingbola","year":"2025","journal-title":"NPJ Vaccines"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Gupta, D., and Mohan, S. (2023). Influenza vaccine: A review on current scenario and future prospects. J. Genet. Eng. Biotechnol., 21.","DOI":"10.1186\/s43141-023-00581-y"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:58Z","timestamp":1760034838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":140,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["vaccines13090890"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13090890","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}