{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:20:31Z","timestamp":1778548831028,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Canadian Institutes of Health Research","award":["#VR2-172722"],"award-info":[{"award-number":["#VR2-172722"]}]},{"name":"NRC\u2019s Pandemic Response Challenge Program","award":["#VR2-172722"],"award-info":[{"award-number":["#VR2-172722"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Continuous viral evolution of SARS-CoV-2 has resulted in variants capable of immune evasion, vaccine breakthrough infections and increased transmissibility. New vaccines that invoke mucosal immunity may provide a solution to reducing virus transmission. Here, we evaluated the immunogenicity of intranasally administered subunit protein vaccines composed of a stabilized SARS-CoV-2 spike trimer or the receptor binding domain (RBD) adjuvanted with either cholera toxin (CT) or an archaeal lipid mucosal adjuvant (AMVAD). We show robust induction of immunoglobulin (Ig) G and IgA responses in plasma, nasal wash and bronchoalveolar lavage in mice only when adjuvant is used in the vaccine formulation. While the AMVAD adjuvant was more effective at inducing systemic antibodies against the RBD antigen than CT, CT was generally more effective at inducing overall higher IgA and IgG titers against the spike antigen in both systemic and mucosal compartments. Furthermore, vaccination with adjuvanted spike led to superior mucosal IgA responses than with the RBD antigen and produced broadly targeting neutralizing plasma antibodies against ancestral, Delta and Omicron variants in vitro; whereas adjuvanted RBD elicited a narrower antibody response with neutralizing activity only against ancestral and Delta variants. Our study demonstrates that intranasal administration of an adjuvanted protein subunit vaccine in immunologically na\u00efve mice induced both systemic and mucosal neutralizing antibody responses that were most effective at neutralizing SARS-CoV-2 variants when the trimeric spike was used as an antigen compared to RBD.<\/jats:p>","DOI":"10.3390\/vaccines11010030","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:24:53Z","timestamp":1671769493000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of Systemic and Mucosal Humoral Immune Responses to an Adjuvanted Intranasal SARS-CoV-2 Protein Subunit Vaccine Candidate in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariam","family":"Maltseva","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannick","family":"Galipeau","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler M.","family":"Renner","sequence":"additional","affiliation":[{"name":"National Research Council Canada, Human Health Therapeutics, Ottawa, ON K1A 0R6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise","family":"Deschatelets","sequence":"additional","affiliation":[{"name":"National Research Council Canada, Human Health Therapeutics, Ottawa, ON K1A 0R6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-4111","authenticated-orcid":false,"given":"Yves","family":"Durocher","sequence":"additional","affiliation":[{"name":"National Research Council Canada, Human Health Therapeutics, Ottawa, ON K1A 0R6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bassel","family":"Akache","sequence":"additional","affiliation":[{"name":"National Research Council Canada, Human Health Therapeutics, Ottawa, ON K1A 0R6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-3029","authenticated-orcid":false,"given":"Marc-Andr\u00e9","family":"Langlois","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Ottawa Center for Infection, Immunity and Inflammation (CI3), Ottawa, ON K1H 8N5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cele, S., Jackson, L., Khoury, D.S., Khan, K., Moyo-Gwete, T., Tegally, H., San, J.E., Cromer, D., Scheepers, C., and Amoako, D. (2021). SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. medRxiv.","DOI":"10.1101\/2021.12.08.21267417"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1056\/NEJMoa2114114","article-title":"Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar","volume":"385","author":"Chemaitelly","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.chom.2020.11.007","article-title":"Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition","volume":"29","author":"Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S1473-3099(22)00146-3","article-title":"COVID-19 vaccine waning and effectiveness and side-effects of boosters: A prospective community study from the ZOE COVID Study","volume":"22","author":"Menni","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1473-3099(21)00648-4","article-title":"Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: A prospective, longitudinal, cohort study","volume":"22","author":"Singanayagam","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","article-title":"SARS-CoV-2 vaccines in development","volume":"586","author":"Krammer","year":"2020","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines\u2014Fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10492","DOI":"10.1038\/s41598-022-14411-7","article-title":"Transmission of B.1.617.2 Delta variant between vaccinated healthcare workers","volume":"12","author":"Kemp","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"612.e1","DOI":"10.1016\/j.cmi.2021.11.010","article-title":"Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: A multicentre cohort study","volume":"28","author":"Chia","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1056\/NEJMc2108076","article-title":"Breakthrough Infections in BNT162b2-Vaccinated Health Care Workers","volume":"385","author":"Lange","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/s41467-021-21336-8","article-title":"Discrete SARS-CoV-2 antibody titers track with functional humoral stability","volume":"12","author":"Bartsch","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41591-021-01263-3","article-title":"Humoral signatures of protective and pathological SARS-CoV-2 infection in children","volume":"27","author":"Bartsch","year":"2021","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1126\/science.abc5902","article-title":"Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability","volume":"369","author":"Brouwer","year":"2020","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cell.2020.05.025","article-title":"Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients\u2019 B Cells","volume":"182","author":"Cao","year":"2020","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.cell.2020.06.044","article-title":"Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients","volume":"182","author":"Kreer","year":"2020","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1126\/science.abc7520","article-title":"Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model","volume":"369","author":"Rogers","year":"2020","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41586-020-2548-6","article-title":"Potently neutralizing and protective human antibodies against SARS-CoV-2","volume":"584","author":"Zost","year":"2020","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41586-020-2571-7","article-title":"Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike","volume":"584","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2022.02.005","article-title":"Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2","volume":"185","author":"Afkhami","year":"2022","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eabo2523","DOI":"10.1126\/science.abo2523","article-title":"Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses","volume":"378","author":"Mao","year":"2022","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eabn6868","DOI":"10.1126\/scitranslmed.abn6868","article-title":"Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model","volume":"14","author":"Langel","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10359","DOI":"10.1038\/s41598-022-13560-z","article-title":"Intranasal vaccination of hamsters with a Newcastle disease virus vector expressing the S1 subunit protects animals against SARS-CoV-2 disease","volume":"12","author":"Diaz","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hassan, A.O., Feldmann, F., Zhao, H., Curiel, D.T., Okumura, A., Tang-Huau, T.L., Case, J.B., Meade-White, K., Callison, J., and Lovaglio, J. (2021). A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. bioRxiv.","DOI":"10.1101\/2021.01.26.428251"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109400","DOI":"10.1016\/j.celrep.2021.109400","article-title":"A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters","volume":"36","author":"Bricker","year":"2021","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eabh0755","DOI":"10.1126\/scitranslmed.abh0755","article-title":"Intranasal ChAdOx1 nCoV-19\/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models","volume":"13","author":"Purushotham","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"King, R.G., Silva-Sanchez, A., Peel, J.N., Botta, D., Dickson, A.M., Pinto, A.K., Meza-Perez, S., Allie, S.R., Schultz, M.D., and Liu, M. (2021). Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge. Vaccines, 9.","DOI":"10.3390\/vaccines9080881"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103037","DOI":"10.1016\/j.isci.2021.103037","article-title":"Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2","volume":"24","author":"An","year":"2021","journal-title":"iScience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.vaccine.2021.03.006","article-title":"Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse","volume":"39","author":"Du","year":"2021","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eadd4853","DOI":"10.1126\/sciimmunol.add4853","article-title":"Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination","volume":"7","author":"Tang","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9772","DOI":"10.1038\/s41598-022-13819-5","article-title":"Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters","volume":"12","author":"Stark","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cell.2020.08.026","article-title":"A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2","volume":"183","author":"Hassan","year":"2020","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41541-021-00393-6","article-title":"Scientific rationale for developing potent RBD-based vaccines targeting COVID-19","volume":"6","author":"Kleanthous","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cell.2020.12.015","article-title":"COVID-19-neutralizing antibodies predict disease severity and survival","volume":"184","author":"Lam","year":"2021","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","article-title":"Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody","volume":"583","author":"Pinto","year":"2020","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41586-020-2852-1","article-title":"SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies","volume":"588","author":"Barnes","year":"2020","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.cell.2020.09.037","article-title":"Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology","volume":"183","author":"Piccoli","year":"2020","journal-title":"Cell"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1586\/erv.11.196","article-title":"Novel vaccine development strategies for inducing mucosal immunity","volume":"11","author":"Fujkuyama","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12070-009-0044-2","article-title":"Intranasal drug delivery: A novel approach","volume":"61","author":"Chugh","year":"2009","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y.Y., Lai, S.K., So, C., Schneider, C., Cone, R., and Hanes, J. (2011). Mucoadhesive nanoparticles may disrupt the protective human mucus barrier by altering its microstructure. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021547"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1128\/iai.61.11.4637-4644.1993","article-title":"Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: Mode of action and augmenting effect of inflammatory cytokines","volume":"61","author":"McGee","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41586-021-04085-y","article-title":"Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity","volume":"600","author":"Lucas","year":"2021","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/mi.2010.54","article-title":"Mucosal adjuvants and long-term memory development with special focus on CTA1-DD and other ADP-ribosylating toxins","volume":"3","author":"Lycke","year":"2010","journal-title":"Mucosal Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4110\/in.2017.17.1.20","article-title":"Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy","volume":"17","author":"Kim","year":"2017","journal-title":"Immune Netw."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00215-18","DOI":"10.1128\/mSphere.00215-18","article-title":"The Mucosal Vaccine Adjuvant LT(R192G\/L211A) or dmLT","volume":"3","author":"Clements","year":"2018","journal-title":"mSphere"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lewis, D.J., Huo, Z., Barnett, S., Kromann, I., Giemza, R., Galiza, E., Woodrow, M., Thierry-Carstensen, B., Andersen, P., and Novicki, D. (2009). Transient facial nerve paralysis (Bell\u2019s palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006999"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"8622","DOI":"10.1016\/j.vaccine.2007.09.042","article-title":"Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-adjuvanted vaccines","volume":"25","author":"Patel","year":"2007","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Patel, G.B., Zhou, H., Ponce, A., Harris, G., and Chen, W. (2010). Intranasal immunization with an archaeal lipid mucosal vaccine adjuvant and delivery formulation protects against a respiratory pathogen challenge. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015574"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1586\/erv.10.34","article-title":"Archaeal lipid mucosal vaccine adjuvant and delivery system","volume":"9","author":"Patel","year":"2010","journal-title":"Expert Rev. Vaccines"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/10915810802352703","article-title":"Safety of intranasally administered archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) vaccine in mice","volume":"27","author":"Patel","year":"2008","journal-title":"Int. J. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/08982100802129232","article-title":"Structural characterization of archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) formulations prepared by different protocols and their efficacy upon intranasal immunization of mice","volume":"18","author":"Patel","year":"2008","journal-title":"J. Liposome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"21849","DOI":"10.1038\/s41598-021-01363-7","article-title":"Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant","volume":"11","author":"Akache","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Akache, B., Deschatelets, L., Harrison, B.A., Dudani, R., Stark, F.C., Jia, Y., Landi, A., Law, J.L.M., Logan, M., and Hockman, D. (2019). Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins. Vaccines, 7.","DOI":"10.3390\/vaccines7040204"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.4049\/jimmunol.166.3.1885","article-title":"The potent adjuvant activity of archaeosomes correlates to the recruitment and activation of macrophages and dendritic cells In Vivo","volume":"166","author":"Krishnan","year":"2001","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1128\/IAI.68.1.54-63.2000","article-title":"Archaeosome vaccine adjuvants induce strong humoral, cell-mediated, and memory responses: Comparison to conventional liposomes and alum","volume":"68","author":"Krishnan","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1380","DOI":"10.1002\/cti2.1380","article-title":"A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination","volume":"11","author":"Colwill","year":"2022","journal-title":"Clin. Transl. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Demone, J., Maltseva, M., Nourimand, M., Nasr-Sharif, M., Galipeau, Y., Alarcon, E.I., Langlois, M.A., and MacLean, A.M. (2022). Scalable agroinfiltration-based production of SARS-CoV-2 antigens for use in diagnostic assays and subunit vaccines. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0277668"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e142362","DOI":"10.1172\/jci.insight.142362","article-title":"A simple protein-based surrogate neutralization assay for SARS-CoV-2","volume":"5","author":"Abe","year":"2020","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/mi.2014.111","article-title":"Cholera toxin adjuvant promotes a balanced Th1\/Th2\/Th17 response independently of IL-12 and IL-17 by acting on Gsalpha in CD11b+ DCs","volume":"8","author":"Mattsson","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1016\/S2666-5247(21)00267-6","article-title":"Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: A meta-analysis","volume":"3","author":"Cromer","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"Khoury","year":"2021","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1038\/s41467-021-26539-7","article-title":"Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eabn3715","DOI":"10.1126\/scitranslmed.abn3715","article-title":"SARS-CoV-2 S2-targeted vaccination elicits broadly neutralizing antibodies","volume":"14","author":"Ng","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.abc6952","article-title":"A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2","volume":"369","author":"Chi","year":"2020","journal-title":"Science"},{"key":"ref_66","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_67","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_68","doi-asserted-by":"crossref","first-page":"e13100","DOI":"10.1111\/sji.13100","article-title":"Analysis of SARS-CoV-2 haplotypes and genomic sequences during 2020 in Victoria, Australia, in the context of putative deficits in innate immune deaminase anti-viral responses","volume":"94","author":"Lindley","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gorczynski, R.M., Lindley, R.A., Steele, E.J., and Wickramasinghe, N.C. (2021). Nature of Acquired Immune Responses, Epitope Specificity and Resultant Protection from SARS-CoV-2. J. Pers. Med., 11.","DOI":"10.3390\/jpm11121253"},{"key":"ref_70","first-page":"1074","article-title":"Respiratory tract immune response to microbial pathogens","volume":"181","author":"Wilkie","year":"1982","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/imr.13118","article-title":"Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection","volume":"309","author":"Sanders","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41385-022-00511-0","article-title":"Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection","volume":"15","author":"Isho","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMc2209651","article-title":"Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection","volume":"387","author":"Havervall","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jaci.2020.10.040","article-title":"Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19","volume":"147","author":"Cervia","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"eabd2223","DOI":"10.1126\/scitranslmed.abd2223","article-title":"IgA dominates the early neutralizing antibody response to SARS-CoV-2","volume":"13","author":"Sterlin","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1056\/NEJMc2119641","article-title":"Plasma Neutralization of the SARS-CoV-2 Omicron Variant","volume":"386","author":"Schmidt","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1016\/S2213-2600(21)00559-2","article-title":"Omicron variant and booster COVID-19 vaccines","volume":"10","author":"Burki","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41586-021-04388-0","article-title":"Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2","volume":"602","author":"Liu","year":"2022","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/j.cell.2022.04.035","article-title":"Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike","volume":"185","author":"Yamasoba","year":"2022","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41467-021-21665-8","article-title":"Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques","volume":"12","author":"Tan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100252","DOI":"10.1016\/j.xcrm.2021.100252","article-title":"SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses","volume":"2","author":"Mandolesi","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1128\/JVI.79.6.3401-3408.2005","article-title":"B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein","volume":"79","author":"Zhong","year":"2005","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.cell.2020.10.052","article-title":"Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality","volume":"183","author":"Zohar","year":"2020","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"618685","DOI":"10.3389\/fimmu.2020.618685","article-title":"Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals","volume":"11","author":"Butler","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev.immunol.15.1.235","article-title":"Neutralizing antiviral B cell responses","volume":"15","author":"Bachmann","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nri2868","article-title":"Vaccine delivery: A matter of size, geometry, kinetics and molecular patterns","volume":"10","author":"Bachmann","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7809","DOI":"10.1073\/pnas.1503885112","article-title":"Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus","volume":"112","author":"Suzuki","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41392-021-00478-7","article-title":"Characterization of SARS-CoV-2-specific antibodies in COVID-19 patients reveals highly potent neutralizing IgA","volume":"6","author":"Zeng","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_89","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_90","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1016\/j.cell.2021.11.023","article-title":"A defective viral genome strategy elicits broad protective immunity against respiratory viruses","volume":"184","author":"Xiao","year":"2021","journal-title":"Cell"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/1\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:04Z","timestamp":1760147344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/1\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,23]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["vaccines11010030"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11010030","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,23]]}}}