{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:29:04Z","timestamp":1792016944274,"version":"4.4.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Respiratory syncytial virus (RSV) remains a significant global health concern, particularly for infants and young children in developing countries. Despite ongoing research efforts, an effective RSV vaccine has yet to be approved for widespread use. Use of two separate pattern recognition receptor (PRR) agonists as adjuvants in vaccine formulations has shown to enhance the immune response against the antigen. The limitation with the use of two adjuvants is that they need not necessarily bind to PRRs on the same cell. This study evaluates the efficacy of two different dual PRR binding chimeric molecules CL413 (TLR2\/TLR7 agonist) and CL429 (TLR2\/NOD2 agonist) as adjuvants for RSV virus-like particles (VLPs) delivered via the pulmonary route in mice for induction of mucosal and systemic immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BALB\/c mice were immunized twice with the RSV-VLPs alone or adjuvanted with CL413, CL429, mixture of single PRR agonists Pam3CSK4+ L18-MDP or Pam3CSK4+ imiquimod via the pulmonary route. The mixture of single PRR agonists adjuvants was used as control for chimeric adjuvants. Immune responses were evaluated by measuring antibody levels in sera and respiratory tract; cytokine production, B and T cell responses in the lungs and spleen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pulmonary immunization with CL413-adjuvanted VLPs induced robust nasal IgA responses against the RSV F and G proteins, which was not observed for the other adjuvant combinations. CL413 also enhanced serum IgG levels and promoted a balanced Th1\/Th2 response, as evidenced by IgG2a\/IgG1 ratios. CL413 elicited strong pro-inflammatory responses in the lungs of mice, including elevated levels of IFN-\u03b3, TNF-\u03b1, IL-6, and IL-17A. Flow cytometry analysis revealed increased numbers of tissue-resident class-switched B cells in the lungs of mice that were immunized with VLPs adjuvanted with CL413 and CL429. CD4+ and CD8+ T cell responses were also enhanced in both lungs and spleens of mice receiving VLPs adjuvanted with chimeric molecules to various extents. Mice immunized with formalin inactivated RSV (FI-RSV), which are used as the positive control for vaccine induced pathology after RSV challenge developed alveolitis, perivascular infiltration. While all the mice receiving adjuvanted VLP formulations showed protection against lung pathology after RSV challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The lack of pathology, combined with the robust mucosal and systemic immune responses, suggests that pulmonary delivery of adjuvanted RSV-VLPs may provide effective protection without the risk of vaccine-enhanced disease. The study also demonstrates that the chimeric TLR2\/TLR7 agonist CL413 is a promising adjuvant for RSV-VLPs to induce mucosal and systemic immune response and warrant further investigations in more advanced preclinical models.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1561297","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:19:45Z","timestamp":1742195985000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of dual pathogen recognition receptor agonists as adjuvants for respiratory syncytial virus - virus-like particles for pulmonary delivery"],"prefix":"10.3389","volume":"16","author":[{"given":"Ahmedali S.","family":"Mandviwala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Liman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke L. W.","family":"Huckriede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya A.","family":"Arankalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshad P.","family":"Patil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004016","article-title":"An overview of respiratory syncytial virus","volume":"10","author":"Meng","year":"2014","journal-title":"PloS Pathog"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.09.040","article-title":"Report of the WHO technical consultation on the evaluation of respiratory syncytial virus prevention cost effectiveness in low- and middle-income countries, April 7\u20138, 2022","volume":"41","author":"Fitzpatrick","year":"2023","journal-title":"Vaccine"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1457703","article-title":"Global progress in clinical research on human respiratory syncytial virus vaccines","volume":"15","author":"Peng","year":"2024","journal-title":"Front Microbiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s12916-023-02792-z","article-title":"Cost of childhood RSV management and cost-effectiveness of RSV interventions: a systematic review from a low- and middle-income country perspective","volume":"21","author":"Wittenauer","year":"2023","journal-title":"BMC Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/v13122478","article-title":"Immunopathology of RSV: an updated review","volume":"13","author":"Bergeron","year":"2021","journal-title":"Viruses"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/iai.33.3.779-783.1981","article-title":"Infectivity of respiratory syncytial virus by various routes of inoculation","volume":"33","author":"Hall","year":"1981","journal-title":"Infect Immun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"240106","DOI":"10.1183\/16000617.0106-2024","article-title":"Antibody-mediated protection against respiratory syncytial virus in children","volume":"33","author":"Coindy","year":"2024","journal-title":"Eur Respir Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2020.1731468","article-title":"Non-invasive mucosal vaccine delivery: advantages, challenges and the future","volume":"17","author":"Skwarczynski","year":"2020","journal-title":"Expert Opin Drug Delivery"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2024.110194","article-title":"Mucosal delivery of a prefusogenic-F, glycoprotein, and matrix proteins-based virus-like particle respiratory syncytial virus vaccine induces protective immunity as evidenced by challenge studies in mice","volume":"598","author":"Mandviwala","year":"2024","journal-title":"Virology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.07.089","article-title":"Respiratory syncytial virus prefusogenic fusion (F) protein nanoparticle vaccine: Structure, antigenic profile, immunogenicity, and protection","volume":"37","author":"Patel","year":"2019","journal-title":"Vaccine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/vaccines8040607","article-title":"Flexible RSV prefusogenic fusion glycoprotein exposes multiple neutralizing epitopes that may collectively contribute to protective immunity","volume":"8","author":"Patel","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.11.010","article-title":"Mucosal adjuvants","volume":"23","author":"Freytag","year":"2005","journal-title":"Vaccine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/vaccines12020191","article-title":"Vaccine strategies to elicit mucosal immunity","volume":"12","author":"Song","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400478111","article-title":"Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants","volume":"111","author":"Maisonneuve","year":"2014","journal-title":"Proc Natl Acad Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4161\/hv.27147","article-title":"TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines","volume":"10","author":"Hjelm","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.178.11.6715","article-title":"TLR2 directly triggers th1 effector functions","volume":"178","author":"Imanishi","year":"2007","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01673","article-title":"Prefusion RSV F immunization elicits th2-mediated lung pathology in mice when formulated with a th2 (but not a th1\/th2-balanced) adjuvant despite complete viral protection","volume":"11","author":"Eichinger","year":"2020","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.02.043","article-title":"Efficacy and safety of an intranasal virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A in mice and cotton rats","volume":"31","author":"Kamphuis","year":"2013","journal-title":"Vaccine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.06.041","article-title":"Lipopeptide-adjuvanted respiratory syncytial virus virosomes: A safe and immunogenic non-replicating vaccine formulation","volume":"28","author":"Stegmann","year":"2010","journal-title":"Vaccine"},{"key":"B20","doi-asserted-by":"publisher","first-page":"149143","DOI":"10.1016\/j.bbrc.2023.149143","article-title":"CpG ODN enhances the efficacy of F protein vaccine against respiratory syncytial virus infection in the upper respiratory tract via CD4+ T cells","volume":"686","author":"Kawahara","year":"2023","journal-title":"Biochem Biophys Res Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.vaccine.2011.11.054","article-title":"Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands","volume":"30","author":"Shafique","year":"2012","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e61287","DOI":"10.1371\/journal.pone.0061287","article-title":"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","volume":"8","author":"Shafique","year":"2013","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature09737","article-title":"Programming the magnitude and persistence of antibody responses with innate immunity","volume":"470","author":"Kasturi","year":"2011","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.virol.2023.06.001","article-title":"Dual pattern recognition receptor ligands CL401, CL413, and CL429 as adjuvants for inactivated chikungunya virus","volume":"585","author":"Gosavi","year":"2023","journal-title":"Virology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3390\/v14020187","article-title":"Mucosal vaccines, sterilizing immunity, and the future of SARS-coV-2 virulence","volume":"14","author":"Focosi","year":"2022","journal-title":"Viruses"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1159\/000489405","article-title":"Mucosal immune response in nasal-associated lymphoid tissue upon intranasal administration by adjuvants","volume":"10","author":"Takaki","year":"2018","journal-title":"J Innate Immun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6646071","article-title":"The role of innate immunity in pulmonary infections","volume":"2021","author":"Zhang","year":"2021","journal-title":"BioMed Res Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.5.2852-2860.1996","article-title":"Respiratory synctial virus infection in BALB\/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern","volume":"70","author":"Waris","year":"1996","journal-title":"J Virol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.20944\/preprints202404.0513.v1","article-title":"Immunogenicity evaluation of respiratory syncytial virus prefusogenic-F based virus-like-particles consisting of G and M proteins in mice","author":"Mandviwala","year":"2024","journal-title":"Preprints (Basel)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00334.2015","article-title":"Flow-cytometric method for simultaneous analysis of mouse lung epithelial, endothelial, and hematopoietic lineage cells","volume":"310","author":"Singer","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23690","article-title":"Best practices for preparing a single cell suspension from solid tissues for flow cytometry","volume":"95","author":"Reichard","year":"2019","journal-title":"Cytomet Part A"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Epidemiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"9","DOI":"10.4049\/jimmunol.1601775","article-title":"Inducing mucosal igA: A challenge for vaccine adjuvants and delivery systems","volume":"199","author":"Boyaka","year":"2017","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-32389-8","article-title":"SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals","volume":"13","author":"Sano","year":"2022","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"crossref","first-page":"105823","DOI":"10.1016\/j.antiviral.2024.105823","article-title":"Unmasking the potential of secretory IgA and its pivotal role in protection from respiratory viruses","volume":"223","author":"Sinha","year":"2024","journal-title":"Antiviral Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/immuno2040036","article-title":"Harnessing nasal immunity with igA to prevent respiratory infections","volume":"2","author":"Joseph","year":"2022","journal-title":"Immuno"},{"key":"B37","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1128\/CMR.00090-16","article-title":"The human immune response to respiratory syncytial virus infection","volume":"30","author":"Russell","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.chom.2021.11.006","article-title":"Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates","volume":"30","author":"Zohar","year":"2022","journal-title":"Cell Host Microbe"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.65","article-title":"IgG subclass co-expression brings harmony to the quartet model of murine IgG function","volume":"94","author":"Collins","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201412-2256OC","article-title":"Impaired antibody-mediated protection and defective igA B-cell memory in experimental infection of adults with respiratory syncytial virus","volume":"191","author":"Habibi","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.ade0424","article-title":"A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine","volume":"14","author":"Chang","year":"2022","journal-title":"Sci Transl Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.016","article-title":"B cell responses: cell interaction dynamics and decisions","volume":"177","author":"Cyster","year":"2019","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","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":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.29","article-title":"Cytokine responses in primary and secondary respiratory syncytial virus infections","volume":"79","author":"Ugonna","year":"2016","journal-title":"Pediatr Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.170.3.1039","article-title":"Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes","volume":"170","author":"Coffman","year":"1989","journal-title":"J Exp Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: putting innate immunity to work","volume":"33","author":"Coffman","year":"2010","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e60","DOI":"10.1038\/emi.2013.58","article-title":"IL-17 cytokines in immunity and inflammation","volume":"2","author":"Jin","year":"2013","journal-title":"Emerg Microbes Infect"},{"key":"B48","doi-asserted-by":"publisher","first-page":"59","DOI":"10.4049\/immunohorizons.2000067","article-title":"Tissue resident memory T cells in the lungs protect against acute respiratory syncytial virus infection","volume":"5","author":"Luangrath","year":"2021","journal-title":"Immunohorizons"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-014-8540-1","article-title":"The CD4 T cell response to respiratory syncytial virus infection","volume":"59","author":"Christiaansen","year":"2014","journal-title":"Immunol Res"},{"key":"B50","doi-asserted-by":"crossref","DOI":"10.1038\/s41385-021-00461-z","article-title":"Tissue resident memory T cells in the respiratory tract","volume":"15","author":"Zheng","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.8.1239","article-title":"Pulmonary immunity and immunopathology: Lessons from respiratory syncytial virus","volume":"7","author":"Olson","year":"2008","journal-title":"Expert Rev Vaccines"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00678","article-title":"The CD8 T cell response to respiratory virus infections","volume":"9","author":"Schmidt","year":"2018","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"crossref","DOI":"10.1038\/mi.2011.62","article-title":"Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection","volume":"5","author":"Loebbermann","year":"2012","journal-title":"Mucosal Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(03)00107-9","article-title":"Granzyme B: Pro-apoptotic, antiviral and antitumor functions","volume":"15","author":"Trapani","year":"2003","journal-title":"Curr Opin Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0180073","article-title":"Combination of poly I:C and Pam3CSK4 enhances activation of B cells in vitro and boosts antibody responses to protein vaccines in vivo","volume":"12","author":"Weir","year":"2017","journal-title":"PloS One"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168446","article-title":"Human in vitro modeling identifies adjuvant combinations that unlock antigen cross-presentation and promote T-helper 1 development in newborns, adults and elders","volume":"436","author":"Thomas","year":"2024","journal-title":"J Mol Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01627","article-title":"TLR2 agonistic small molecules: detailed structure-activity relationship, applications, and future prospects","volume":"64","author":"Kaur","year":"2021","journal-title":"J Med Chem"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6308","article-title":"The Mucosal Adjuvant Macrophage-Activating Lipopeptide-2 Directly Stimulates B Lymphocytes via the TLR2 without the Need of Accessory Cells","volume":"174","author":"Borsutzky","year":"2005","journal-title":"J Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1159\/000355217","article-title":"Innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated TLR7 ligand","volume":"6","author":"Wu","year":"2014","journal-title":"J Innate Immun"},{"key":"B60","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/mtm.2015.18","article-title":"Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates","volume":"2","author":"Pierantoni","year":"2015","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B61","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.3390\/vaccines10122078","article-title":"Microparticle RSV vaccines presenting the G protein CX3C chemokine motif in the context of TLR signaling induce protective th1 immune responses and prevent pulmonary eosinophilia post-challenge","volume":"10","author":"Powell","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-31709-2","article-title":"CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns","volume":"13","author":"van Haren","year":"2022","journal-title":"Nat Commun"},{"key":"B63","doi-asserted-by":"publisher","first-page":"121378","DOI":"10.1016\/j.ijpharm.2021.121378","article-title":"Combined delivery of TLR2 and TLR7 agonists by Nanostructured lipid carriers induces potent vaccine adjuvant activity in mice","volume":"613","author":"Kaur","year":"2022","journal-title":"Int J Pharm"},{"key":"B64","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nri.2017.90","article-title":"Type 2 immunity in tissue repair and fibrosis","volume":"18","author":"Gieseck","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02061","article-title":"The dual nature of type I and type II interferons","volume":"9","author":"Lee","year":"2018","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1800","article-title":"Pathogen molecular pattern receptor agonists: Treating cancer by mimicking infection","volume":"25","author":"Aleynick","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: mechanisms and platforms","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0186854","article-title":"Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus","volume":"12","author":"Sastry","year":"2017","journal-title":"PloS One"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09085-1","article-title":"Systematic comparison of respiratory syncytial virus-induced memory B cell responses in two anatomical compartments","volume":"10","author":"Shehata","year":"2019","journal-title":"Nat Commun"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T follicular helper cell biology: A decade of discovery and diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2933","article-title":"Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells","volume":"361","author":"DiToro","year":"2018","journal-title":"Science"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1586\/eri.10.39","article-title":"Association of IL-13 in respiratory syncytial virus-induced pulmonary disease: Still a promising target","volume":"8","author":"Mukherjee","year":"2010","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B73","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.180.4.2376","article-title":"IL-13 Is Required for Eosinophil Entry into the Lung during Respiratory Syncytial Virus Vaccine-Enhanced Disease","volume":"180","author":"Castilow","year":"2008","journal-title":"J\u00a0Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e21823","DOI":"10.1371\/journal.pone.0021823","article-title":"A novel inactivated intranasal respiratory syncytial virus vaccine promotes viral clearance without th2 associated vaccine-enhanced disease","volume":"6","author":"Lindell","year":"2011","journal-title":"PloS One"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.279","article-title":"Tumor necrosis factor blockade and the risk of viral infection","volume":"6","author":"Kim","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.03.089","article-title":"The effects of IL-6 and TNF-alpha as molecular adjuvants on immune responses to FMDV and maturation of dendritic cells by DNA vaccination","volume":"26","author":"Su","year":"2008","journal-title":"Vaccine"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/nri3152","article-title":"Expanding roles for CD4+ T cells in immunity to viruses","volume":"12","author":"Swain","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200209)32:9<2562::AID-IMMU2562>3.0.CO;2-4","article-title":"Pulmonary T cells induced by respiratory syncytial virus are functional and can make an important contribution to long-lived protective immunity","volume":"32","author":"Ostler","year":"2002","journal-title":"Eur J Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"109401","DOI":"10.1016\/j.celrep.2021.109401","article-title":"A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant","volume":"36","author":"Zhao","year":"2021","journal-title":"Cell Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.10.004","article-title":"Applications of immunomodulatory immune synergies to adjuvant discovery and vaccine development","volume":"37","author":"Tom","year":"2019","journal-title":"Trends Biotechnol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890260207","article-title":"Primary respiratory syncytial virus infection in mice","volume":"26","author":"Graham","year":"1988","journal-title":"J Med Virol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00720-15","article-title":"Novel respiratory syncytial virus-like particle vaccine composed of the postfusion and prefusion conformations of the F glycoprotein","volume":"23","author":"Cimica","year":"2016","journal-title":"Clin Vaccine Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1382318","article-title":"Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias","volume":"15","author":"Eberlein","year":"2024","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1561297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T09:50:34Z","timestamp":1742377834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1561297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":83,"alternative-id":["10.3389\/fimmu.2025.1561297"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1561297","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"article-number":"1561297"}}