{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:14:56Z","timestamp":1791476096117,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w\/o\/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040510","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:42:01Z","timestamp":1744616521000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response"],"prefix":"10.3390","volume":"17","author":[{"given":"Emmanuel","family":"Adediran","sequence":"first","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanisha","family":"Arte","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4780-9658","authenticated-orcid":false,"given":"Dedeepya","family":"Pasupuleti","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-4157","authenticated-orcid":false,"given":"Sharon","family":"Vijayanand","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revanth","family":"Singh","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3290-0603","authenticated-orcid":false,"given":"Parth","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahek","family":"Gulani","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarae","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Uddin","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-8770","authenticated-orcid":false,"given":"Susu M.","family":"Zughaier","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1021\/acsinfecdis.8b00206","article-title":"A Perspective on Nanoparticle Universal Influenza Vaccines","volume":"4","author":"Deng","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dou, D., Revol, R., \u00d6stbye, H., Wang, H., and Daniels, R. (2018). Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01581"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1002\/biot.201400393","article-title":"Emerging influenza viruses and the prospect of a universal influenza virus vaccine","volume":"10","author":"Krammer","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1473-3099(07)70029-4","article-title":"Transmission of influenza A in human beings","volume":"7","author":"Brankston","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/infdis\/jis773","article-title":"Exposure to Influenza Virus Aerosols During Routine Patient Care","volume":"207","author":"Bischoff","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1016\/j.vaccine.2020.07.043","article-title":"Immunogenicity and efficacy comparison of MDCK cell-based and egg-based live attenuated influenza vaccines of H5 and H7 subtypes in ferrets","volume":"38","author":"Yeolekar","year":"2020","journal-title":"Vaccine"},{"key":"ref_7","first-page":"1141","article-title":"Vaccine approaches conferring cross-protection against influenza viruses. Expert Rev","volume":"16","author":"Vemula","year":"2017","journal-title":"Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4161\/hv.7.0.14560","article-title":"Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine","volume":"7","author":"Durando","year":"2011","journal-title":"Hum. Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tian, Y., Bhide, Y.C., Woerdenbag, H.J., Huckriede, A.L.W., Frijlink, H.W., Hinrichs, W.L.J., and Visser, J.C. (2020). Development of an Orodispersible Film Containing Stabilized Influenza Vaccine. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030245"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1016\/j.vaccine.2015.06.061","article-title":"Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance","volume":"33","author":"Burgess","year":"2015","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4155\/tde-2016-0008","article-title":"Vaccine delivery: Where polymer chemistry meets immunology","volume":"7","author":"Shae","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ymeth.2006.05.017","article-title":"Microparticle-based technologies for vaccines","volume":"40","author":"Singh","year":"2006","journal-title":"Methods"},{"key":"ref_13","first-page":"210","article-title":"Interaction of Microspheres with Blood Constituents: I. Uptake of Polystyrene Spheres by Monocytes and Granulocytes and Effect on Immune Responsiveness of Lymphocytes","volume":"37","author":"Kanke","year":"1983","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/0142-9612(88)90033-6","article-title":"Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage","volume":"9","author":"Tabata","year":"1988","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0169-409X(98)00012-X","article-title":"Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines","volume":"32","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shah, S., Patel, P., Ferguson, A., Bagwe, P., Kale, A., Adediran, E., Singh, R., Arte, T., Pasupuleti, D., and Uddin, M.N. (2024). Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model. Vaccines, 12.","DOI":"10.3390\/vaccines12070720"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121919","DOI":"10.1016\/j.ijpharm.2022.121919","article-title":"Nanoparticle formulation of the fusion protein virus like particles of respiratory syncytial virus stimulates enhanced in vitro antigen presentation and autophagy","volume":"623","author":"Menon","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gomes, K.B., Vijayanand, S., Bagwe, P., Menon, I., Kale, A., Patil, S., Kang, S.-M., Uddin, M.N., and D\u2019souza, M.J. (2023). Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles. IJMS, 24.","DOI":"10.3390\/ijms241310612"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vijayanand, S., Patil, S., Menon, I., Gomes, K.B., Kale, A., Bagwe, P., Uddin, M.N., Zughaier, S.M., and D\u2019souza, M.J. (2023). An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030895"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"589833","DOI":"10.3389\/fimmu.2020.589833","article-title":"Adjuvants for Coronavirus Vaccines","volume":"11","author":"Liang","year":"2020","journal-title":"Front Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-021-02145-0","article-title":"AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice","volume":"22","author":"Nian","year":"2021","journal-title":"Aaps Pharmscitech"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wilkins, A.L., Kazmin, D., Napolitani, G., Clutterbuck, E.A., Pulendran, B., Siegrist, C.-A., and Pollard, A.J. (2017). AS03- and MF59-Adjuvanted Influenza Vaccines in Children. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01760"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jconrel.2015.05.278","article-title":"Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection","volume":"210","author":"Kim","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1080\/21645515.2016.1171440","article-title":"The success of microneedle-mediated vaccine delivery into skin","volume":"12","author":"Marshall","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0140-6736(17)30575-5","article-title":"The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): A randomised, partly blinded, placebo-controlled, phase 1 trial","volume":"390","author":"Rouphael","year":"2017","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sekiya, T., Ohno, M., Nomura, N., Handabile, C., Shingai, M., Jackson, D.C., Brown, L.E., and Kida, H. (2021). Selecting and Using the Appropriate Influenza Vaccine for Each Individual. Viruses, 13.","DOI":"10.3390\/v13060971"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Calzas, C., and Chevalier, C. (2019). Innovative Mucosal Vaccine Formulations Against Influenza A Virus Infections. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01605"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","unstructured":"Vijayanand, S., Patil, S., Joshi, D., Menon, I., Gomes, K.B., Kale, A., Bagwe, P., Yacoub, S., Uddin, M.N., and D\u2019souza, M.J. (2022). Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus. Vaccines, 10.","DOI":"10.3390\/vaccines10091491"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Drioli, E., and Giorno, L. (2016). Encapsulation Efficiency. Encyclopedia of Membranes [Internet], Springer. Available online: http:\/\/link.springer.com\/10.1007\/978-3-662-44324-8_1945.","DOI":"10.1007\/978-3-642-40872-4"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Roberts, J.M., Milo, S., and Metcalf, D.G. (2024). Harnessing the Power of Our Immune System: The Antimicrobial and Antibiofilm Properties of Nitric Oxide. Microorganisms, 12.","DOI":"10.3390\/microorganisms12122543"},{"key":"ref_32","first-page":"557","article-title":"Emerging and reemerging respiratory viral infections up to COVID-19. Turk","volume":"50","year":"2020","journal-title":"J. Med Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/cid\/ciab931","article-title":"Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children","volume":"75","author":"Olson","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1586\/erv.10.89","article-title":"Nano-microparticles as immune adjuvants: Correlating particle sizes and the resultant immune responses","volume":"9","author":"Oyewumi","year":"2010","journal-title":"Expert Rev. Vaccines"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/S0264-410X(96)00016-3","article-title":"Size effect on the antibody production induced by biodegradable microspheres containing antigen","volume":"14","author":"Nakaoka","year":"1996","journal-title":"Vaccine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymeth.2006.05.016","article-title":"Pathogen recognition and development of particulate vaccines: Does size matter?","volume":"40","author":"Xiang","year":"2006","journal-title":"Methods"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, Z., and Roche, P.A. (2015). Macropinocytosis in phagocytes: Regulation of MHC class-II-restricted antigen presentation in dendritic cells. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00001"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"El-Hammadi, M.M., and Arias, J.L. (2022). Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines. Nanomaterials, 12.","DOI":"10.3390\/nano12030354"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2174\/1573413714666180313130235","article-title":"Suggested Procedures for the Reproducible Synthesis of Poly(d,l-lactideco-glycolide) Nanoparticles Using the Emulsification Solvent Diffusion Platform","volume":"14","author":"Haque","year":"2018","journal-title":"Curr. Nanosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/0264-410X(95)00127-M","article-title":"Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans","volume":"13","author":"Kilbourne","year":"1995","journal-title":"Vaccine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118168","DOI":"10.1016\/j.carbpol.2021.118168","article-title":"Hyaluronic acid based microneedle array: Recent applications in drug delivery and cosmetology","volume":"267","author":"Saha","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s13346-015-0228-0","article-title":"Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature","volume":"5","author":"Vassilieva","year":"2015","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","unstructured":"Trincado, V., Gala, R.P., and Morales, J.O. (2021). Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems. Vaccines, 9.","DOI":"10.3390\/vaccines9101177"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Carty, S.A., Riese, M.J., and Koretzky, G.A. (2018). T-Cell Immunity. Hematology [Internet], Elsevier. Available online: https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/B9780323357623000214.","DOI":"10.1016\/B978-0-323-35762-3.00021-4"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Vijayanand, S., Patil, S., Bagwe, P., Singh, R., Adediran, E., and D\u2019Souza, M.J. (2025). Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza. Vaccines, 13.","DOI":"10.3390\/vaccines13030282"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Domnich, A., Manini, I., Panatto, D., Calabr\u00f2, G.E., and Montomoli, E. (2020). Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials. Vaccines, 8.","DOI":"10.3390\/vaccines8020325"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/jps.23019","article-title":"Dissolvable microneedle patches for the delivery of cell-culture-derived influenza vaccine antigens","volume":"101","author":"Kommareddy","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Howard, F.H.N., Kwan, A., Winder, N., Mughal, A., Collado-Rojas, C., and Muthana, M. (2022). Understanding Immune Responses to Viruses\u2014Do Underlying Th1\/Th2 Cell Biases Predict Outcome?. Viruses, 14.","DOI":"10.3390\/v14071493"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kim, B.M., Kim, Y.-H., Ngo, H.V., Nguyen, H.D., Park, C., and Lee, B.-J. (2025). Enhanced and Prolonged Immunogenicity in Mice of Thermally Stabilized Fatty Acid-Conjugated Vaccine Antigen. Vaccines, 13.","DOI":"10.3390\/vaccines13020168"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hinkula, J., Nystr\u00f6m, S., Devito, C., Br\u00e5ve, A., and Applequist, S.E. (2019). Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice. Vaccines, 7.","DOI":"10.3390\/vaccines7030064"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kasten-Jolly, J., and Lawrence, D.A. (2024). Cellular and Molecular Immunity to Influenza Viruses and Vaccines. Vaccines, 12.","DOI":"10.20944\/preprints202403.1671.v1"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tsang, T.K., Lam, K.T., Liu, Y., Fang, V.J., Mu, X., Leung, N.H.L., Peiris, J.S.M., Leung, G.M., Cowling, B.J., and Tu, W. (2022). Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study. BMC Med., 20.","DOI":"10.1186\/s12916-022-02429-7"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Patil, S., Vijayanand, S., Menon, I., Gomes, K.B., Kale, A., Bagwe, P., Yacoub, S., Uddin, M.N., and D\u2019Souza, M.J. (2023). Adjuvanted-SARS-CoV-2 Spike Protein-Based Microparticulate Vaccine Delivered by Dissolving Microneedles Induces Humoral, Mucosal, and Cellular Immune Responses in Mice. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081131"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/adfm.201201512","article-title":"Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination","volume":"23","author":"DeMuth","year":"2023","journal-title":"Adv. Funct. Mater."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s11095-024-03665-7","article-title":"Intradermal Vaccination with PLGA Nanoparticles via Dissolving Microneedles and Classical Injection Needles","volume":"41","author":"Lee","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/btm2.10103","article-title":"Self-healing encapsulation and controlled release of vaccine antigens from PLGA microparticles delivered by microneedle patches","volume":"4","author":"Mazzara","year":"2019","journal-title":"Bioeng. Transl. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/510\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:17Z","timestamp":1760029997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,12]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["pharmaceutics17040510"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17040510","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,12]]}}}