Induction of protective immune responses at respiratory mucosal sites

References

• Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat Rev Immunol. 2006;6(2):148–12. doi:10.1038/nri1777.
   PubMed Web of Science ®Google Scholar
• Xu H, Cai L, Hufnagel S, Cui Z. Intranasal vaccine: factors to consider in research and development. Int J Pharm. 2021;609:121180. doi:10.1016/j.ijpharm.2021.121180.
   PubMedGoogle Scholar
• Bennett JV, Fernandez de Castro J, Valdespino-Gomez JL, MdL G-G, Islas-Romero R, Echaniz-Aviles G, Jimenez-Corona A, Sepulveda-Amor J. Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren. Bull World Health Organ. 2002;80(10):806–812.
   PubMed Web of Science ®Google Scholar
• Hellfritzsch M, Scherließ R. Mucosal vaccination via the respiratory tract. Pharmaceutics. 2019;11(8). Epub 20190801. doi: 10.3390/pharmaceutics11080375. PubMed PMID: 31374959; PubMed Central PMCID: PMC6723941.
   PubMed Web of Science ®Google Scholar
• Nakahashi-Ouchida R, Fujihashi K, Kurashima Y, Yuki Y, Kiyono H. Nasal vaccines: solutions for respiratory infectious diseases. Trends Mol Med. 2023;29(2):124–140. doi:10.1016/j.molmed.2022.10.009.
   PubMed Web of Science ®Google Scholar
• Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nat Rev Immunol. 2017;17(1):7–20. Epub 20161128. doi: 10.1038/nri.2016.117. PubMed PMID: 27890913; PubMed Central PMCID: PMC5480291.
   PubMed Web of Science ®Google Scholar
• Kurono Y. The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines. Auris Nasus Larynx. 2022;49(1):1–10. Epub 20210723. doi:10.1016/j.anl.2021.07.003. PubMed PMID: 34304944.
   PubMed Web of Science ®Google Scholar
• Dillon A, LO DD. M cells: intelligent engineering of mucosal immune surveillance. Front Immunol. 2019;10. doi:10.3389/fimmu.2019.01499.
   Web of Science ®Google Scholar
• Steffen U, Koeleman CA, Sokolova MV, Bang H, Kleyer A, Rech J, Unterweger H, Schicht M, Garreis F, Hahn J, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun. 2020;11(1):120. doi:10.1038/s41467-019-13992-8.
   PubMed Web of Science ®Google Scholar
• Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal Immunol. 2011;4(6):590–597. doi:10.1038/mi.2011.39.
   PubMed Web of Science ®Google Scholar
• Mettelman RC, Allen EK, Thomas PG. Mucosal immune responses to infection and vaccination in the respiratory tract. Immunity. 2022;55(5):749–780. doi:10.1016/j.immuni.2022.04.013. PubMed PMID: 35545027; PubMed Central PMCID: PMC9087965.
   PubMed Web of Science ®Google Scholar
• Tsai CJY, Loh JMS, Fujihashi K, Kiyono H. Mucosal vaccination: onward and upward. Expert Rev Vaccines. 2023;22(1):885–899. Epub 20231017. doi: 10.1080/14760584.2023.2268724. PubMed PMID: 37817433.
   PubMed Web of Science ®Google Scholar
• Lavelle EC, Ward RW. Mucosal vaccines—fortifying the frontiers. Nat Rev Immunol. 2022;22(4):236–250. doi:10.1038/s41577-021-00583-2.
   PubMed Web of Science ®Google Scholar
• Sallusto F, Lanzavecchia A, Araki K, Ahmed R. From vaccines to memory and back. Immunity. 2010;33(4):451–463. doi:10.1016/j.immuni.2010.10.008. PubMed PMID: 21029957; PubMed Central PMCID: PMC3760154.
   PubMed Web of Science ®Google Scholar
• Rhee JH, Lee SE, Kim SY. Mucosal vaccine adjuvants update. Clin Exp Vaccine Res. 2012;1(1):50–63. doi:10.7774/cevr.2012.1.1.50.
   PubMedGoogle Scholar
• Lehmann R, Müller MM, Klassert TE, Driesch D, Stock M, Heinrich A, Conrad T, Moore C, Schier UK, Guthke R, et al. Differential regulation of the transcriptomic and secretomic landscape of sensor and effector functions of human airway epithelial cells. Mucosal Immunol. 2018;11(3):627–642. doi:10.1038/mi.2017.100.
   PubMed Web of Science ®Google Scholar
• Takamura S, Kato S, Motozono C, Shimaoka T, Ueha S, Matsuo K, Miyauchi K, Masumoto T, Katsushima A, Nakayama T, et al. Interstitial-resident memory CD8+ T cells sustain frontline epithelial memory in the lung. J Exp Med. 2019;216(12):2736–2747. doi:10.1084/jem.20190557.
   PubMed Web of Science ®Google Scholar
• Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol. 2015;16(1):27–35. doi:10.1038/ni.3045. PubMed PMID: 25521682; PubMed Central PMCID: PMC4318521.
   PubMed Web of Science ®Google Scholar
• Amersfoort J, Eelen G, Carmeliet P. Immunomodulation by endothelial cells—partnering up with the immune system? Nat Rev Immunol. 2022;22(9):576–588. doi:10.1038/s41577-022-00694-4.
   PubMed Web of Science ®Google Scholar
• Button B, Cai L-H, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science. 2012;337(6097):937–941. doi:10.1126/science.1223012.
   PubMed Web of Science ®Google Scholar
• Wallace LE, Liu M, van Kuppeveld Fjm, de Vries E, de Haan Cam, van Kuppeveld FJM, de Haan CAM. Respiratory mucus as a virus-host range determinant. Trends Microbiol. 2021;29(11):983–992. doi:10.1016/j.tim.2021.03.014.
   PubMed Web of Science ®Google Scholar
• Vasquez-Martínez N, Guillen D, Moreno-Mendieta SA, Sanchez S, Rodríguez-Sanoja R. The role of mucoadhesion and mucopenetration in the immune response induced by polymer-based mucosal adjuvants. Polymers. 2023;15(7):1615. doi:10.3390/polym15071615.
   PubMed Web of Science ®Google Scholar
• Konrad FM, Wohlert J, Gamper-Tsigaras J, Ngamsri K-C, Reutershan J. How adhesion molecule patterns change while neutrophils traffic through the lung during inflammation. Mediators Inflamm. 2019;2019:1208086. doi:10.1155/2019/1208086.
   PubMed Web of Science ®Google Scholar
• Castanheira FV, Kubes P. Neutrophils during SARS‐CoV‐2 infection: Friend or foe? Immunol Rev. 2023;314(1):399–412. doi:10.1111/imr.13175.
   PubMed Web of Science ®Google Scholar
• Capucetti A, Albano F, Bonecchi R. Multiple roles for chemokines in neutrophil biology. Front Immunol. 2020;11:11. doi:10.3389/fimmu.2020.01259.
   PubMed Web of Science ®Google Scholar
• Chan L, Morovati S, Karimi N, Alizadeh K, Vanderkamp S, Kakish JE, Bridle BW, Karimi K. Neutrophil functional heterogeneity and implications for viral infections and treatments. Cells. 2022;11(8). Epub 20220413. doi: 10.3390/cells11081322. PubMed PMID: 35456003; PubMed Central PMCID: PMC9025666.
   Web of Science ®Google Scholar
• Zhang R, Sun C, Han Y, Huang L, Sheng H, Wang J, Zhang Y, Lai J, Yuan J, Chen X, et al. Neutrophil autophagy and NETosis in COVID-19: perspectives. Autophagy. 2023;19(3):758–767. doi:10.1080/15548627.2022.2099206.
   PubMed Web of Science ®Google Scholar
• Huot N, Planchais C, Rosenbaum P, Contreras V, Jacquelin B, Petitdemange C, Lazzerini M, Beaumont E, Orta-Resendiz A, Rey FA, et al. SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells. Nat Immunol. 2023;24(12):2068–79. doi:10.1038/s41590-023-01661-4.
   PubMed Web of Science ®Google Scholar
• Evren E, Ringqvist E, Doisne J-M, Thaller A, Sleiers N, Flavell RA, Di Santo JP, Willinger T. CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages. J Exp Med. 2022;219(2):e20210987. doi:10.1084/jem.20210987.
   PubMed Web of Science ®Google Scholar
• Lee MJ, Blish CA. Defining the role of natural killer cells in COVID-19. Nat Immunol. 2023;24(10):1628–1638. doi:10.1038/s41590-023-01560-8.
   PubMed Web of Science ®Google Scholar
• Hou F, Xiao K, Tang L, Xie L. Diversity of macrophages in lung homeostasis and diseases. Front Immunol. 2021;12:753940. doi:10.3389/fimmu.2021.753940.
   PubMed Web of Science ®Google Scholar
• Nachbagauer R, Feser J, Naficy A, Bernstein DI, Guptill J, Walter EB, Berlanda-Scorza F, Stadlbauer D, Wilson PC, Aydillo T, et al. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat Med. 2021;27(1):106–114. Epub 20201207. doi: 10.1038/s41591-020-1118-7. PubMed PMID: 33288923.
   PubMed Web of Science ®Google Scholar
• Wang T, Zhang J, Wang Y, Li Y, Wang L, Yu Y, Yao Y. Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs. Nat Immunol. 2023;24(3):423–438. doi:10.1038/s41590-023-01428-x.
   PubMed Web of Science ®Google Scholar
• Ding C, Shrestha R, Zhu X, Geller AE, Wu S, Woeste MR, Li W, Wang H, Yuan F, Xu R, et al. Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis. Nat Immunol. 2023;24(2):239–254. doi:10.1038/s41590-022-01388-8.
   PubMed Web of Science ®Google Scholar
• Abassi Z, Knaney Y, Karram T, Heyman SN. The lung macrophage in SARS-CoV-2 infection: a friend or a foe? Front Immunol. 2020;11:1312. doi:10.3389/fimmu.2020.01312.
   PubMed Web of Science ®Google Scholar
• Wang X, Guan F, Miller H, Byazrova MG, Candotti F, Benlagha K, Camara NOS, Lei J, Filatov A, Liu C, et al. The role of dendritic cells in COVID-19 infection. Emerging Microbes Infect. 2023;12(1):2195019. doi:10.1080/22221751.2023.2195019.
   PubMed Web of Science ®Google Scholar
• Gilliet M, Cao W, Liu YJ. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol. 2008;8(8):594–606. doi:10.1038/nri2358. PubMed PMID: 18641647.
   PubMed Web of Science ®Google Scholar
• Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM. et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20(6):375–388. Epub 20200304. doi: 10.1038/s41577-020-0285-6. PubMed PMID: 32132681; PubMed Central PMCID: PMC7186935.
   PubMed Web of Science ®Google Scholar
• Netea MG, Quintin J, Van Der Meer JW. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9(5):355–361. doi:10.1016/j.chom.2011.04.006.
   PubMed Web of Science ®Google Scholar
• Netea MG, Joosten LAB, Latz E, Mills KHG, Natoli G, Stunnenberg HG, O’Neill LAJ, Xavier RJ. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352(6284):aaf1098. doi:10.1126/science.aaf1098.
   PubMed Web of Science ®Google Scholar
• Ochando J, Mulder WJM, Madsen JC, Netea MG, Duivenvoorden R. Trained immunity—basic concepts and contributions to immunopathology. Nat Rev Nephrol. 2023;19(1):23–37. doi:10.1038/s41581-022-00633-5.
   PubMed Web of Science ®Google Scholar
• Yu D, Zhang J, Wang S. Trained immunity in the mucosal diseases. WIREs Mech Dis. 2022;14(2):e1543. doi:10.1002/wsbm.1543.
   PubMedGoogle Scholar
• Momtazmanesh S, Moghaddam SS, Ghamari S-H, Rad EM, Rezaei N, Shobeiri P, Aali A, Abbasi-Kangevari M, Abbasi-Kangevari Z, Abdelmasseh M, et al. Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the global burden of disease study 2019. eClinicalmedicine. 2023;59:101936. doi:10.1016/j.eclinm.2023.101936.
   PubMedGoogle Scholar
• Kingstad-Bakke B, Lee W, Chandrasekar SS, Gasper DJ, Salas-Quinchucua C, Cleven T, Sullivan JA, Talaat A, Osorio JE, Suresh M, et al. Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants. Proc Natl Acad Sci USA. 2022;119(20):e2118312119. doi:10.1073/pnas.2118312119.
   PubMed Web of Science ®Google Scholar
• Winstead CJ. Follicular helper T cell-mediated mucosal barrier maintenance. Immunol Lett. 2014;162(2, Part A):39–47. doi:10.1016/j.imlet.2014.07.015.
   PubMed Web of Science ®Google Scholar
• Paiva IA, Badolato-Corrêa J, Familiar-Macedo D, de-Oliveira-Pinto LM. Th17 cells in viral infections—friend or foe? Cells. 2021;10(5). Epub 20210511. doi: 10.3390/cells10051159. PubMed PMID: 34064728; PubMed Central PMCID: PMC8151546.
   Web of Science ®Google Scholar
• Skon CN, Lee J-Y, Anderson KG, Masopust D, Hogquist KA, Jameson SC. Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells. Nat Immunol. 2013;14(12):1285–1293. doi:10.1038/ni.2745.
   PubMed Web of Science ®Google Scholar
• Lim JME, Tan AT, Le Bert N, Hang SK, Low JGH, Bertoletti A. SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity. J Exp Med. 2022;219(10). doi:10.1084/jem.20220780.
   Web of Science ®Google Scholar
• Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science. 2014;346(6205):98–101. doi:10.1126/science.1254536.
   PubMed Web of Science ®Google Scholar
• Schreiner D, King CG. CD4+ memory T cells at home in the tissue: mechanisms for health and disease. Front Immunol. 2018;9:2394. Epub 20181016. doi: 10.3389/fimmu.2018.02394. PubMed PMID: 30386342; PubMed Central PMCID: PMC6198086.
   PubMed Web of Science ®Google Scholar
• Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrançois L, Farber DL. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol. 2011;187(11):5510–5514. doi:10.4049/jimmunol.1102243.
   PubMed Web of Science ®Google Scholar
• Moyron-Quiroz JE, Rangel-Moreno J, Kusser K, Hartson L, Sprague F, Goodrich S, Woodland DL, Lund FE, Randall TD. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med. 2004;10(9):927–934. Epub 20040815. doi: 10.1038/nm1091. PubMed PMID: 15311275.
   PubMed Web of Science ®Google Scholar
• Allie SR, Bradley JE, Mudunuru U, Schultz MD, Graf BA, Lund FE, Randall TD. The establishment of resident memory B cells in the lung requires local antigen encounter. Nat Immunol. 2019;20(1):97–108. doi:10.1038/s41590-018-0260-6.
   PubMed Web of Science ®Google Scholar
• Tan HX, Juno JA, Esterbauer R, Kelly HG, Wragg KM, Konstandopoulos P, Alcantara S, Alvarado C, Jones R, Starkey G. et al. Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles. Sci Immunol. 2022;7(67):eabf5314. Epub 20220128. doi: 10.1126/sciimmunol.abf5314. PubMed PMID: 35089815.
   PubMed Web of Science ®Google Scholar
• Onodera T, Takahashi Y, Yokoi Y, Ato M, Kodama Y, Hachimura S, Kurosaki T, Kobayashi K. Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection. Proc Natl Acad Sci USA. 2012;109(7):2485–2490. doi:10.1073/pnas.1115369109.
   PubMed Web of Science ®Google Scholar
• Vujanic A, Sutton P, Snibson KJ, Yen HH, Scheerlinck JP. Mucosal vaccination: lung versus nose. Vet Immunol Immunopathol. 2012;148(1–2):172–177. Epub 20110323. doi: 10.1016/j.vetimm.2011.03.004. PubMed PMID: 21492942.
   PubMed Web of Science ®Google Scholar
• Pilapitiya D, Wheatley AK, Tan H-X. Mucosal vaccines for SARS-CoV-2: triumph of hope over experience. EBioMedicine. 2023;92:104585. doi:10.1016/j.ebiom.2023.104585.
   PubMed Web of Science ®Google Scholar
• Paris AL, Colomb E, Verrier B, Anjuère F, Monge C. Sublingual vaccination and delivery systems. J Control Release. 2021;332:553–562. Epub 20210315. doi: 10.1016/j.jconrel.2021.03.017. PubMed PMID: 33737202.
   PubMed Web of Science ®Google Scholar
• van Ginkel Fw, Jackson RJ, Yuki Y, McGhee JR, van Ginkel FW. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol. 2000;165(9):4778–482. doi:10.4049/jimmunol.165.9.4778.
   PubMed Web of Science ®Google Scholar
• Kraan H, Vrieling H, Czerkinsky C, Jiskoot W, Kersten G, Amorij J-P. Buccal and sublingual vaccine delivery. J Controlled Release. 2014;190:580–592. doi:10.1016/j.jconrel.2014.05.060.
   PubMed Web of Science ®Google Scholar
• El-Sherbiny IM, El-Baz NM, Yacoub MH. Inhaled nano- and microparticles for drug delivery. Glob Cardiol Sci Pract. 2015;2015(1):2. Epub 20150331. doi: 10.5339/gcsp.2015.2. PubMed PMID: 26779496; PubMed Central PMCID: PMC4386009.
   PubMedGoogle Scholar
• Jabbal S, Poli G, Lipworth B. Does size really matter?: relationship of particle size to lung deposition and exhaled fraction. J Allergy Clin Immunol. 2017;139(6):2013–2014. e1. doi:10.1016/j.jaci.2016.11.036.
   PubMed Web of Science ®Google Scholar
• Marasini N, Kaminskas LM. Subunit-based mucosal vaccine delivery systems for pulmonary delivery-are they feasible? Drug Dev Ind Pharm. 2019;45(6):882–894. doi:10.1080/03639045.2019.1583758.
   PubMed Web of Science ®Google Scholar
• Fromen CA, Rahhal TB, Robbins GR, Kai MP, Shen TW, Luft JC, DeSimone JM. Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells. Nanomed Nanotechnol Biol Med. 2016;12(3):677–687. Epub 20151201. doi:10.1016/j.nano.2015.11.002. PubMed PMID: 26656533; PubMed Central PMCID: PMC4839472.
   PubMed Web of Science ®Google Scholar
• Moyano DF, Goldsmith M, Solfiell DJ, Landesman-Milo D, Miranda OR, Peer D, Rotello VM. Nanoparticle hydrophobicity dictates immune response. J Am Chem Soc. 2012;134(9):3965–3967. doi:10.1021/ja2108905.
   PubMed Web of Science ®Google Scholar
• Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261–279. doi:10.1038/nrd.2017.243.
   PubMed Web of Science ®Google Scholar
• Wendorf J, Chesko J, Kazzaz J, Ugozzoli M, Vajdy M, O’Hagan D, Singh M. A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin. 2008;4(1):44–49. Epub 20070815. doi:10.4161/hv.4.1.4886. PubMed PMID: 18438105.
   PubMed Web of Science ®Google Scholar
• da Silva Aj, Zangirolami TC, Novo-Mansur MT, Giordano Rde C, Martins EA, Silva AJD. Live bacterial vaccine vectors: an overview. Braz J Microbiol. 2014;45(4):1117–11129. Epub 20150304. doi: 10.1590/s1517-83822014000400001. PubMed PMID: 25763014; PubMed Central PMCID: PMC4323283.
   PubMed Web of Science ®Google Scholar
• Treanor JJ, Kotloff K, Betts RF, Belshe R, Newman F, Iacuzio D, Wittes J, Bryant M. Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza a (H1N1), a (H3N2), and B viruses. Vaccine. 1999;18(9–10):899–906. doi:10.1016/s0264-410x(99)00334-5. PubMed PMID: 10580204.
   PubMed Web of Science ®Google Scholar
• Pulendran B, Arunachalam P, O’Hagan DT. Emerging concepts in the science of vaccine adjuvants. Nat Rev Drug Discov. 2021;20(6):454–475. doi:10.1038/s41573-021-00163-y.
   PubMed Web of Science ®Google Scholar
• Zhao T, Cai Y, Jiang Y, He X, Wei Y, Yu Y, Tian X. Vaccine adjuvants: mechanisms and platforms. Signal Transduct Target Ther. 2023;8(1):283. doi:10.1038/s41392-023-01557-7.
   PubMed Web of Science ®Google Scholar
• Guy B. The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol. 2007;5(7):396–397. doi:10.1038/nrmicro1681.
   Web of Science ®Google Scholar
• Li H, Nookala S, Re F. Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol. 2007;178(8):5271–5276. doi:10.4049/jimmunol.178.8.5271. PubMed PMID: 17404311.
   PubMed Web of Science ®Google Scholar
• Seubert A, Calabro S, Santini L, Galli B, Genovese A, Valentini S, Aprea S, Colaprico A, D’Oro U, Giuliani MM. et al. Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88. Proc Natl Acad Sci USA. 2011;108(27):11169–11174. doi:10.1073/pnas.1107941108.
   PubMed Web of Science ®Google Scholar
• Didierlaurent AM, Laupèze B, Di Pasquale A, Hergli N, Collignon C, Garçon N. Adjuvant system AS01: helping to overcome the challenges of modern vaccines. Expert Rev Vaccines. 2017;16(1):55–63. doi:10.1080/14760584.2016.1213632.
   PubMed Web of Science ®Google Scholar
• Cohet C, van der Most R, Bauchau V, Bekkat-Berkani R, Doherty TM, Schuind A, Tavares Da Silva F, Rappuoli R, Garçon N, Innis BL, et al. Safety of AS03-adjuvanted influenza vaccines: A review of the evidence. Vaccine. 2019;37(23):3006–3021. doi:10.1016/j.vaccine.2019.04.048.
   PubMed Web of Science ®Google Scholar
• Garçon N, Morel S, Didierlaurent A, Descamps D, Wettendorff M, Van Mechelen M. Development of an AS04-adjuvanted HPV vaccine with the adjuvant system approach. BioDrugs. 2011;25(4):217–26. doi:10.2165/11591760-000000000-00000.
   PubMed Web of Science ®Google Scholar
• Campbell JD, Cho Y, Foster ML, Kanzler H, Kachura MA, Lum JA, Ratcliffe MJ, Sathe A, Leishman AJ, Bahl A. et al. CpG-containing immunostimulatory DNA sequences elicit TNF-α–dependent toxicity in rodents but not in humans. J Clin Invest. 2009;119(9):2564–2576. doi:10.1172/JCI38294.
   PubMed Web of Science ®Google Scholar
• Stertman L, Palm AE, Zarnegar B, Carow B, Lunderius Andersson C, Magnusson SE, Carnrot C, Shinde V, Smith G, Glenn G. et al. The matrix-M™ adjuvant: A critical component of vaccines for the 21 st century. Hum Vaccin Immunother. 2023;19(1):2189885. Epub 20230427. doi:10.1080/21645515.2023.2189885. PubMed PMID: 37113023; PubMed Central PMCID: PMC10158541.
   PubMed Web of Science ®Google Scholar
• He X, Chen X, Wang H, Du G, Sun X. Recent advances in respiratory immunization: a focus on COVID-19 vaccines. J Controlled Release. 2023;355:655–674. doi:10.1016/j.jconrel.2023.02.011.
   PubMed Web of Science ®Google Scholar
• Stillman ZS, Decker GE, Dworzak MR, Bloch ED, Fromen CA. Aluminum-based metal–organic framework nanoparticles as pulmonary vaccine adjuvants. J Nanobiotechnol. 2023;21(1):39. doi:10.1186/s12951-023-01782-w.
   PubMed Web of Science ®Google Scholar
• Xu H, Alzhrani RF, Warnken ZN, Thakkar SG, Zeng M, Smyth HDC, Williams RO, Cui Z. Immunogenicity of antigen adjuvanted with AS04 and its deposition in the upper respiratory tract after intranasal administration. Mol Pharm. 2020;17(9):3259–3269. doi:10.1021/acs.molpharmaceut.0c00372.
   PubMedGoogle Scholar
• Thakkar SG, Warnken ZN, Alzhrani RF, Valdes SA, Aldayel AM, Xu H, Williams RO, Cui Z. Intranasal immunization with aluminum salt-adjuvanted dry powder vaccine. J Controlled Release. 2018;292:111–118. doi:10.1016/j.jconrel.2018.10.020.
   PubMed Web of Science ®Google Scholar
• Pedersen G, Major D, Roseby S, Wood J, Madhun AS, Cox RJ. Matrix‐M adjuvanted virosomal H5N1 vaccine confers protection against lethal viral challenge in a murine model. Influenza Other Respi Viruses. 2011;5(6):426–437. doi:10.1111/j.1750-2659.2011.00256.x.
   PubMed Web of Science ®Google Scholar
• Shafique M, Meijerhof T, Wilschut J, de Haan A, Renukaradhya GJ. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses. PLOS ONE. 2013;8(4):e61287. Epub 20130408. doi:10.1371/journal.pone.0061287. PubMed PMID: 23593453; PubMed Central PMCID: PMC3620164.
   PubMed Web of Science ®Google Scholar
• Cataldi A, Yevsa T, Vilte DA, Schulze K, Castro-Parodi M, Larzábal M, Ibarra C, Mercado EC, Guzmán CA. Efficient immune responses against Intimin and EspB of enterohaemorragic Escherichia coli after intranasal vaccination using the TLR2/6 agonist MALP-2 as adjuvant. Vaccine. 2008;26(44):5662–5667. doi:10.1016/j.vaccine.2008.07.027.
   PubMed Web of Science ®Google Scholar
• Sabbaghi A, Malek M, Abdolahi S, Miri SM, Alizadeh L, Samadi M, Mohebbi SR, Ghaemi A. A formulated poly (I: C)/CCL21 as an effective mucosal adjuvant for gamma-irradiated influenza vaccine. Virol J. 2021;18(1):201. Epub 20211009. doi:10.1186/s12985-021-01672-3. PubMed PMID: 34627297; PubMed Central PMCID: PMC8501930.
   PubMed Web of Science ®Google Scholar
• Strindelius L, Filler M, Sjöholm I. Mucosal immunization with purified flagellin from Salmonella induces systemic and mucosal immune responses in C3H/HeJ mice. Vaccine. 2004;22(27):3797–3808. doi:10.1016/j.vaccine.2003.12.035.
   PubMed Web of Science ®Google Scholar
• Puth S, Hong SH, Park MJ, Lee HH, Lee YS, Jeong K, Kang I-C, Koh JT, Moon B, Park SC. et al. Mucosal immunization with a flagellin-adjuvanted Hgp44 vaccine enhances protective immune responses in a murine porphyromonas gingivalis infection model. Hum Vaccines Immunother. 2017;13(12):2794–2803. doi:10.1080/21645515.2017.1327109.
   PubMed Web of Science ®Google Scholar
• Kawahara E, Yamamoto S, Shibata T, Hirai T, Yoshioka Y. CpG ODN enhances the efficacy of F protein vaccine against respiratory syncytial virus infection in the upper respiratory tract via CD4+ T cells. Biochem Bioph Res Co. 2023;686:149143. doi:10.1016/j.bbrc.2023.149143.
   PubMed Web of Science ®Google Scholar
• McCluskie MJ, Davis HL. CpG DNA as mucosal adjuvant. Vaccine. 1999;18(3):231–237. doi:10.1016/S0264-410X(99)00194-2.
   PubMed Web of Science ®Google Scholar
• Atalis A, Keenum MC, Pandey B, Beach A, Pradhan P, Vantucci C, O’Farrell L, Noel R, Jain R, Hosten J. et al. Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine. J Controlled Release. 2022;347:476–488. doi:10.1016/j.jconrel.2022.05.023.
   PubMed Web of Science ®Google Scholar
• Wong PT, Goff PH, Sun RJ, Ruge MJ, Ermler ME, Sebring A, O’Konek JJ, Landers JJ, Janczak KW, Sun W. et al. Combined intranasal nanoemulsion and RIG-I Activating RNA adjuvants enhance mucosal, humoral, and cellular immunity to influenza virus. Mol Pharm. 2021;18(2):679–698. Epub 20200615. doi: 10.1021/acs.molpharmaceut.0c00315. PubMed PMID: 32491861.
   PubMedGoogle Scholar
• Jangra S, Landers JJ, Laghlali G, Rathnasinghe R, Warang P, Park SC, O’Konek JJ, Singh G, Janczak KW, García-Sastre A. et al. Multicomponent intranasal adjuvant for mucosal and durable systemic SARS-CoV-2 immunity in young and aged mice. NPJ Vaccines. 2023;8(1):96. Epub 20230629. doi:10.1038/s41541-023-00691-1. PubMed PMID: 37386041; PubMed Central PMCID: PMC10310740.
   PubMed Web of Science ®Google Scholar
• Jangra S, Landers JJ, Rathnasinghe R, O’Konek JJ, Janczak KW, Cascalho M, Kennedy AA, Tai AW, Baker JR, Schotsaert M. et al. A combination adjuvant for the induction of potent antiviral immune responses for a recombinant SARS-CoV-2 protein vaccine. Front Immunol. 2021;12:729189. Epub 20210916. doi:10.3389/fimmu.2021.729189. PubMed PMID: 34603303; PubMed Central PMCID: PMC8481386.
   PubMed Web of Science ®Google Scholar
• Jangra S, De Vrieze J, Choi A, Rathnasinghe R, Laghlali G, Uvyn A, Van Herck S, Nuhn L, Deswarte K, Zhong Z. et al. Sterilizing Immunity against SARS-CoV-2 Infection in mice by a single-shot and lipid amphiphile imidazoquinoline TLR7/8 agonist-adjuvanted recombinant spike protein vaccine*. Angew Chem Int Ed Engl. 2021;60(17):9467–9473. Epub 20210311. doi: 10.1002/anie.202015362. PubMed PMID: 33464672; PubMed Central PMCID: PMC8014308.
   PubMed Web of Science ®Google Scholar
• Qadri F, Akhtar M, Bhuiyan TR, Chowdhury MI, Ahmed T, Rafique TA, Khan A, Rahman SIA, Khanam F, Lundgren A. et al. Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2020;20(2):208–219. Epub 20191119. doi:10.1016/s1473-3099(19)30571-7. PubMed PMID: 31757774; PubMed Central PMCID: PMC6990395.
   PubMed Web of Science ®Google Scholar
• Lebens M, Terrinoni M, Karlsson SL, Larena M, Gustafsson-Hedberg T, Källgård S, Nygren E, Holmgren J. Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae. Vaccine. 2016;34(18):2121–2128. doi:10.1016/j.vaccine.2016.03.002.
   PubMed Web of Science ®Google Scholar
• Agren LC, Ekman L, Löwenadler B, Lycke NY. Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. J Immunol (Baltimore, Md: 1950). 1997;158(8):3936–3946. doi:10.4049/jimmunol.158.8.3936.
   PubMed Web of Science ®Google Scholar
• Schussek S, Bernasconi V, Mattsson J, Wenzel UA, Strömberg A, Gribonika I, Schön K, Lycke NY. The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization. Mucosal Immunol. 2020;13(3):545–557. doi:10.1038/s41385-020-0253-2.
   PubMed Web of Science ®Google Scholar
• Pan S-C, Hsu W-T, Lee W-S, Wang N-C, Chen T-J, Liu M-C, Pai H-C, Hsu Y-S, Chang M, Hsieh S-M, et al. A double-blind, randomized controlled trial to evaluate the safety and immunogenicity of an intranasally administered trivalent inactivated influenza vaccine with the adjuvant LTh(αK): a phase II study. Vaccine. 2020;38(5):1048–1056. doi:10.1016/j.vaccine.2019.11.047.
   PubMed Web of Science ®Google Scholar
• Pan SC, Hsieh SM, Lin CF, Hsu YS, Chang M, Chang SC. A randomized, double-blind, controlled clinical trial to evaluate the safety and immunogenicity of an intranasally administered trivalent inactivated influenza vaccine with adjuvant LTh(αK): a phase I study. Vaccine. 2019;37(14):1994–2003. Epub 20190302. doi:10.1016/j.vaccine.2019.02.006. PubMed PMID: 30837170.
   PubMed Web of Science ®Google Scholar
• Gao Y, Guo Y. Research progress in the development of natural-product-based mucosal vaccine adjuvants. Front Immunol. 2023;14:1152855. Epub 20230405. doi:10.3389/fimmu.2023.1152855. PubMed PMID: 37090704; PubMed Central PMCID: PMC10113501.
   PubMed Web of Science ®Google Scholar
• Sun B, Yu S, Zhao D, Guo S, Wang X, Zhao K. Polysaccharides as vaccine adjuvants. Vaccine. 2018;36(35):5226–5234. doi:10.1016/j.vaccine.2018.07.040.
   PubMed Web of Science ®Google Scholar
• Yu M, Yang Y, Zhu C, Guo S, Gan Y. Advances in the transepithelial transport of nanoparticles. Drug Discov Today. 2016;21(7):1155–1161. doi:10.1016/j.drudis.2016.05.007.
   PubMed Web of Science ®Google Scholar
• Kumar US, Afjei R, Ferrara K, Massoud TF, Paulmurugan R. Gold-nanostar-chitosan-mediated delivery of SARS-CoV-2 DNA vaccine for respiratory mucosal immunization: development and proof-of-principle. ACS Nano. 2021;15(11):17582–17601. doi:10.1021/acsnano.1c05002.
   PubMed Web of Science ®Google Scholar
• Svindland SC, Jul-Larsen Å, Pathirana R, Andersen S, Madhun A, Montomoli E, Jabbal‐Gill I, Cox RJ. The mucosal and systemic immune responses elicited by a chitosan-adjuvanted intranasal influenza H5N1 vaccine. Influenza Resp Viruses. 2012;6(2):90–100. Epub 20110712. doi:10.1111/j.1750-2659.2011.00271.x. PubMed PMID: 21749672; PubMed Central PMCID: PMC4942079.
   PubMed Web of Science ®Google Scholar
• Gao Y, Gong X, Yu S, Jin Z, Ruan Q, Zhang C, Zhao K. Immune enhancement of N-2-hydroxypropyl trimethyl ammonium chloride chitosan/carboxymethyl chitosan nanoparticles vaccine. Int J Biol Macromol. 2022;220:183–192. doi:10.1016/j.ijbiomac.2022.08.073.
   PubMed Web of Science ®Google Scholar
• Johansson E-L, Wassen L, Holmgren J, Jertborn M, Rudin A, Clements JD. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect Immun. 2001;69(12):7481–746. doi:10.1128/iai.69.12.7481-7486.2001.
   PubMed Web of Science ®Google Scholar