{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:35:22Z","timestamp":1771331722619,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00042"],"award-info":[{"award-number":["75N93019C00042"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201800048C"],"award-info":[{"award-number":["HHSN272201800048C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["PG19-61078-01"],"award-info":[{"award-number":["PG19-61078-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Principal Investigator DAC","award":["75N93019C00042"],"award-info":[{"award-number":["75N93019C00042"]}]},{"name":"Principal Investigator DAC","award":["HHSN272201800048C"],"award-info":[{"award-number":["HHSN272201800048C"]}]},{"name":"Principal Investigator DAC","award":["PG19-61078-01"],"award-info":[{"award-number":["PG19-61078-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal\/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4\/7 adjuvant (Fos47) enhances systemic and local\/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM\/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.<\/jats:p>","DOI":"10.3390\/vaccines10101694","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T06:13:27Z","timestamp":1665468807000},"page":"1694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination"],"prefix":"10.3390","volume":"10","author":[{"given":"Fumi","family":"Sato-Kaneko","sequence":"first","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyin","family":"Yao","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fitzgerald S.","family":"Lao","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiya","family":"Sako","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine","family":"Jin","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-7827","authenticated-orcid":false,"given":"Nikunj M.","family":"Shukla","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard B.","family":"Cottam","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Chan","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masiel M.","family":"Belsuzarri","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis A.","family":"Carson","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-8348","authenticated-orcid":false,"given":"Tomoko","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0809, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s13054-019-2491-9","article-title":"Influenza virus-related critical illness: Prevention, diagnosis, treatment","volume":"23","author":"Chow","year":"2019","journal-title":"Crit. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13054-019-2539-x","article-title":"Influenza virus-related critical illness: Pathophysiology and epidemiology","volume":"23","author":"Kalil","year":"2019","journal-title":"Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1126\/science.abg9857","article-title":"Scent of a vaccine","volume":"373","author":"Lund","year":"2021","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41573-019-0056-x","article-title":"Next-generation influenza vaccines: Opportunities and challenges","volume":"19","author":"Wei","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1177\/0194599820982633","article-title":"COVID-19 Vaccines May Not Prevent Nasal SARS-CoV-2 Infection and Asymptomatic Transmission","volume":"164","author":"Bleier","year":"2021","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1001\/jama.2021.18143","article-title":"Trying to Block SARS-CoV-2 Transmission With Intranasal Vaccines","volume":"326","author":"Rubin","year":"2021","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41385-022-00517-8","article-title":"Dealing with a mucosal viral pandemic: Lessons from COVID-19 vaccines","volume":"15","author":"Mouro","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1128\/jvi.69.2.1339-1343.1995","article-title":"Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies","volume":"69","author":"Mazanec","year":"1995","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fimmu.2018.00320","article-title":"Host Immune Response to Influenza A Virus Infection","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev-immunol-032414-112315","article-title":"Exploiting Mucosal Immunity for Antiviral Vaccines","volume":"34","author":"Iwasaki","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/eji.1830210602","article-title":"Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules","volume":"21","author":"Tamura","year":"1991","journal-title":"Eur. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0264-410X(90)90250-P","article-title":"Functional role of respiratory tract haemagglutinin-specific IgA antibodies in protection against influenza","volume":"8","author":"Tamura","year":"1990","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"Pulendran","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1080\/21645515.2017.1415684","article-title":"Adjuvanted influenza vaccines","volume":"14","author":"Tregoning","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200258","DOI":"10.1183\/16000617.0258-2020","article-title":"Influenza vaccination: Protecting the most vulnerable","volume":"30","author":"Tanner","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nguyen-Contant, P., Sangster, M.Y., and Topham, D.J. (2021). Squalene-Based Influenza Vaccine Adjuvants and Their Impact on the Hemagglutinin-Specific B Cell Response. Pathogens, 10.","DOI":"10.3390\/pathogens10030355"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/MOP.0000000000000868","article-title":"Toward precision adjuvants: Optimizing science and safety","volume":"32","author":"Nanishi","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1586\/14760584.6.5.699","article-title":"MF59 is a safe and potent vaccine adjuvant that enhances protection against influenza virus infection","volume":"6","year":"2007","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.coi.2017.07.010","article-title":"Towards an evidence based approach for the development of adjuvanted vaccines","volume":"47","author":"Friedland","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S429","DOI":"10.1093\/infdis\/jiab387","article-title":"Herpes Zoster Vaccines","volume":"224","author":"Harbecke","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ward, B.J., Gobeil, P., S\u00e9guin, A., Atkins, J., Boulay, I., Charbonneau, P.-Y., Couture, M., D\u2019Aoust, M.-A., Dhaliwall, J., and Finkle, C. (2020). Phase 1 trial of a Candidate Recombinant Virus-Like Particle Vaccine for Covid-19 Disease Produced in Plants. medRxiv.","DOI":"10.1101\/2020.11.04.20226282"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa030595","article-title":"Use of the inactivated intranasal influenza vaccine and the risk of Bell\u2019s palsy in Switzerland","volume":"350","author":"Mutsch","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1056\/NEJMp048006","article-title":"Nasal vaccination, Escherichia coli enterotoxin, and Bell\u2019s palsy","volume":"350","author":"Couch","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_26","unstructured":"(2022, August 28). Bell Palsy Following Intranasal Influenza Vaccination. Available online: https:\/\/www.who.int\/groups\/global-advisory-committee-on-vaccine-safety\/topics\/bell-s-palsy-following-intranasal-vaccination."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103841","DOI":"10.1016\/j.ebiom.2022.103841","article-title":"Intranasal COVID-19 vaccines: From bench to bed","volume":"76","author":"Alu","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1021\/bc900054q","article-title":"Synthesis and immunological characterization of toll-like receptor 7 agonistic conjugates","volume":"20","author":"Chan","year":"2009","journal-title":"Bioconjug Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1021\/jm301694x","article-title":"Identification of substituted pyrimido[5,4-b]indoles as selective Toll-like receptor 4 ligands","volume":"56","author":"Chan","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1128\/JVI.03337-14","article-title":"Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses","volume":"89","author":"Goff","year":"2015","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e01050-17","DOI":"10.1128\/JVI.01050-17","article-title":"Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice","volume":"91","author":"Goff","year":"2017","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.3389\/fimmu.2020.01207","article-title":"A Novel Synthetic Dual Agonistic Liposomal TLR4\/7 Adjuvant Promotes Broad Immune Responses in an Influenza Vaccine With Minimal Reactogenicity","volume":"11","author":"Yao","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1080\/14760584.2018.1495565","article-title":"Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention","volume":"17","author":"Lecrenier","year":"2018","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2025718118","DOI":"10.1073\/pnas.2025718118","article-title":"Mitochondria-dependent synthetic small-molecule vaccine adjuvants for influenza virus infection","volume":"118","author":"Yao","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_36","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/bib\/bbn017","article-title":"MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences","volume":"9","author":"Kumar","year":"2008","journal-title":"Brief. Bioinform"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nprot.2014.005","article-title":"Intravascular staining for discrimination of vascular and tissue leukocytes","volume":"9","author":"Anderson","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymeth.2019.01.018","article-title":"Multiplexing protein and gene level measurements on a single Luminex platform","volume":"158","author":"Cook","year":"2019","journal-title":"Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fcimb.2019.00344","article-title":"The Quest for a Truly Universal Influenza Vaccine","volume":"9","author":"Jang","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.virol.2010.12.016","article-title":"Contributions of humoral and cellular immunity to vaccine-induced protection in humans","volume":"411","author":"Amanna","year":"2011","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41577-021-00578-z","article-title":"Immunological mechanisms of vaccine-induced protection against COVID-19 in humans","volume":"21","author":"Sadarangani","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A guide to vaccinology: From basic principles to new developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eaas9673","DOI":"10.1126\/sciimmunol.aas9673","article-title":"Location, location, location: Tissue resident memory T cells in mice and humans","volume":"4","author":"Szabo","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines-fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e85832","DOI":"10.1172\/jci.insight.85832","article-title":"Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection","volume":"1","author":"Zens","year":"2016","journal-title":"JCI Insight"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"808527","DOI":"10.3389\/fimmu.2021.808527","article-title":"Potentiating Lung Mucosal Immunity Through Intranasal Vaccination","volume":"12","author":"Nelson","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.coviro.2020.09.006","article-title":"Anti-viral protective capacity of tissue resident memory T cells","volume":"46","author":"Paik","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/cmi.2010.22","article-title":"The cytokine milieu in the interplay of pathogenic Th1\/Th17 cells and regulatory T cells in autoimmune disease","volume":"7","author":"Leung","year":"2010","journal-title":"Cell Mol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nri705","article-title":"T(H)1 and T(H)2 cells: A historical perspective","volume":"2","author":"Liew","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/sji.12288","article-title":"Induction of Local Secretory IgA and Multifunctional CD4(+) T-helper Cells Following Intranasal Immunization with a H5N1 Whole Inactivated Influenza Virus Vaccine in BALB\/c Mice","volume":"81","author":"Trondsen","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41590-018-0260-6","article-title":"The establishment of resident memory B cells in the lung requires local antigen encounter","volume":"20","author":"Allie","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eabj5129","DOI":"10.1126\/sciimmunol.abj5129","article-title":"Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA","volume":"6","author":"Oh","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hellfritzsch, M., and Scherliess, R. (2019). Mucosal Vaccination via the Respiratory Tract. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080375"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.immuni.2022.04.013","article-title":"Mucosal immune responses to infection and vaccination in the respiratory tract","volume":"55","author":"Mettelman","year":"2022","journal-title":"Immunity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.addr.2005.12.003","article-title":"Needle-free vaccine delivery","volume":"58","author":"Giudice","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_58","first-page":"153","article-title":"Cholera toxin-a foe & a friend","volume":"133","author":"Sanchez","year":"2011","journal-title":"Indian J. Med. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1086\/314827","article-title":"Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity","volume":"180","author":"Kurono","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3109\/08820131003622635","article-title":"Secretory IgA: Arresting microbial pathogens at epithelial borders","volume":"39","author":"Mantis","year":"2010","journal-title":"Immunol. Invest."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.4049\/jimmunol.168.6.2930","article-title":"Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines","volume":"168","author":"Asahi","year":"2002","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.4161\/hv.25458","article-title":"Intranasal vaccination with an inactivated whole influenza virus vaccine induces strong antibody responses in serum and nasal mucus of healthy adults","volume":"9","author":"Ainai","year":"2013","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/jmv.20173","article-title":"Secretory IgA antibodies provide cross-protection against infection with different strains of influenza B virus","volume":"74","author":"Yoshikawa","year":"2004","journal-title":"J. Med. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/eji.1830140414","article-title":"Cross-protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity","volume":"14","author":"Liew","year":"1984","journal-title":"Eur. J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1038\/s41467-021-27063-4","article-title":"Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization","volume":"12","author":"Lapuente","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"L833","DOI":"10.1152\/ajplung.00173.2001","article-title":"Distribution of intranasal instillations in mice: Effects of volume, time, body position, and anesthesia","volume":"282","author":"Southam","year":"2002","journal-title":"Am. J. Physiol Lung Cell Mol. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/10\/1694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:40Z","timestamp":1760143780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/10\/1694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":67,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["vaccines10101694"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10101694","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}