{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T01:59:39Z","timestamp":1791683979717,"version":"4.3.4"},"reference-count":158,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Respiratory syncytial virus (RSV) remains a leading cause of acute lower respiratory tract infections globally, particularly affecting infants, older adults, and immunocompromised individuals. While recent advances in prophylaxis, such as long-acting monoclonal antibodies and maternal immunization, offer promise for prevention, therapeutic options for active infection remain limited. Severe RSV disease is often driven not solely by viral replication but by dysregulated host immune responses, including excessive cytokine production, T helper type 2 (Th2) and T helper type 17 (Th17) cell polarization, and impaired interferon signaling. RSV has evolved sophisticated immune evasion strategies, such as inhibition of dendritic cell maturation, degradation of signal transducer and activator of transcription 2 (STAT2) via nonstructural proteins 1 and 2 (NS1\/NS2), and interference with pattern recognition receptor signaling, particularly Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. These mechanisms result in attenuated innate immune responses and defective adaptive immunity, contributing to viral persistence, immunopathology, and recurrent infections. Moreover, age-dependent vulnerabilities, such as immune immaturity in infants and immunosenescence in older adults, exacerbate disease severity. Excessive immune activation leads to bronchiolitis, airway remodeling, and long-term sequelae including wheezing and asthma. Emerging immunomodulatory therapies aim to restore immune balance, targeting cytokines (e.g., interleukin-6 [IL-6], interleukin-1 beta [IL-1\u03b2]), the Janus kinase\u2013signal transducer and activator of the transcription (JAK-STAT) pathway, or inflammasome activity. Host-directed therapies and direct-acting antivirals are also under investigation. A better understanding of RSV\u2013host immune interactions is critical for optimizing therapeutic strategies and designing effective vaccines. This review synthesizes current knowledge on RSV immunopathogenesis and highlights immunomodulation as a promising frontier for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/microorganisms13081876","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T07:53:44Z","timestamp":1754985224000},"page":"1876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Immunomodulation in Respiratory Syncytial Virus Infection: Mechanisms, Therapeutic Targets, and Clinical Implications"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-811X","authenticated-orcid":false,"given":"Vasiliki Epameinondas","family":"Georgakopoulou","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Laiko General Hospital, National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-8489","authenticated-orcid":false,"given":"Vassiliki C.","family":"Pitiriga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School of Athens, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/S0140-6736(17)30938-8","article-title":"Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study","volume":"390","author":"Shi","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s40266-024-01118-9","article-title":"Respiratory Syncytial Virus Infection in Older Adults: An Update","volume":"41","author":"Alfano","year":"2024","journal-title":"Drugs Aging"},{"key":"ref_3","first-page":"e36342","article-title":"Respiratory Syncytial Virus: A Comprehensive Review of Transmission, Pathophysiology, and Manifestation","volume":"15","author":"Kaler","year":"2023","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1164\/rccm.201412-2256OC","article-title":"Mechanisms of Severe Acute Influenza Consortium Investigators. 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":"ref_5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.imbio.2007.10.008","article-title":"Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins","volume":"213","author":"Dalpke","year":"2008","journal-title":"Immunobiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5353","DOI":"10.1128\/JVI.79.9.5353-5362.2005","article-title":"Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-\u03baB, and proinflammatory cytokines","volume":"79","author":"Spann","year":"2005","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1086\/315319","article-title":"Respiratory syncytial virus infection induces expression of the anti-apoptosis gene IEX-1L in human respiratory epithelial cells","volume":"181","author":"Domachowske","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.immuni.2019.08.007","article-title":"Immunological Lessons from Respiratory Syncytial Virus Vaccine Development","volume":"51","author":"Ruckwardt","year":"2019","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.coviro.2013.05.005","article-title":"Protective and dysregulated T cell immunity in RSV infection","volume":"3","author":"Openshaw","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lambert, L., Sagfors, A.M., Openshaw, P.J., and Culley, F.J. (2014). Immunity to RSV in early life. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00466"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1067\/S0022-3476(03)00508-0","article-title":"Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection","volume":"143","author":"Welliver","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_12","first-page":"500","article-title":"High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections","volume":"71","author":"Lee","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJMoa2207566","article-title":"Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults","volume":"388","author":"Falsey","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1056\/NEJMoa2213836","article-title":"Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults","volume":"388","author":"Walsh","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1056\/NEJMoa2209604","article-title":"Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults","volume":"388","author":"Papi","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13613-025-01460-0","article-title":"Nirsevimab prophylaxis on pediatric intensive care hospitalization for severe acute bronchiolitis: A clinical and economic analysis","volume":"15","author":"Touati","year":"2025","journal-title":"Ann. Intensive Care"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bergeron, H.C., and Tripp, R.A. (2021). Immunopathology of RSV: An Updated Review. Viruses, 13.","DOI":"10.3390\/v13122478"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.tim.2013.02.004","article-title":"Respiratory syncytial virus interaction with human airway epithelium","volume":"21","author":"Villenave","year":"2013","journal-title":"Trends Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/80833","article-title":"Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus","volume":"1","author":"Popova","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1177\/1753425912444479","article-title":"Role of human TLR4 in respiratory syncytial virus-induced NF-\u03baB activation, viral entry and replication","volume":"18","author":"Marr","year":"2012","journal-title":"Innate Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/JVI.01740-06","article-title":"Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells","volume":"81","author":"Liu","year":"2007","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/jmv.20556","article-title":"Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections","volume":"78","author":"Okabayashi","year":"2006","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.20140825","article-title":"Alveolar macrophage-derivAlveolar macrophage-derived ed type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes","volume":"212","author":"Goritzka","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sebina, I., and Phipps, S. (2020). The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis. Viruses, 12.","DOI":"10.3390\/v12080808"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/JVI.06209-11","article-title":"Natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection","volume":"86","author":"Li","year":"2012","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1112","DOI":"10.1002\/cti2.1112","article-title":"Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation","volume":"9","author":"Lakerveld","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/ni.2131","article-title":"Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus","volume":"12","author":"Monticelli","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12931-021-01799-5","article-title":"Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation","volume":"22","author":"Warren","year":"2021","journal-title":"Respir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Malinczak, C.A., Schuler, C.F., Duran, A.J., Rasky, A.J., Mire, M.M., N\u00fa\u00f1ez, G., Lukacs, N.W., and Fonseca, W. (2021). NLRP3-inflammasome inhibition during respiratory virus infection abrogates lung immunopathology and long-term airway disease development. Viruses, 13.","DOI":"10.3390\/v13040692"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12985-023-02194-w","article-title":"Oxidative stress and ROS-mediated cellular events in RSV infection: Potential protective roles of antioxidants","volume":"20","author":"Yang","year":"2023","journal-title":"Virol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1165\/rcmb.2016-0375TR","article-title":"The role of nucleotide-binding oligomerization domain-like receptors in pulmonary infection","volume":"57","author":"Wiese","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Godkowicz, M., and Druszczy\u0144ska, M. (2022). NOD1, NOD2, and NLRC5 receptors in antiviral and antimycobacterial immunity. Vaccines, 10.","DOI":"10.3390\/vaccines10091487"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/ni.1782","article-title":"Activation of innate immune antiviral responses by Nod2","volume":"10","author":"Sabbah","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1099\/jgv.0.000401","article-title":"Beyond the inflammasome: Regulatory NOD-like receptor modulation of the host immune response following virus exposure","volume":"97","author":"Eden","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9315","DOI":"10.1128\/JVI.79.14.9315-9319.2005","article-title":"Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha\/beta interferon responsiveness","volume":"79","author":"Lo","year":"2005","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hijano, D.R., Vu, L.D., Kauvar, L.M., Tripp, R.A., Polack, F.P., and Cormier, S.A. (2019). Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00566"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Schmidt, M.E., and Varga, S.M. (2018). The CD8 T Cell Response to Respiratory Virus Infections. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00678"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ruckwardt, T.J., Malloy, A.M., Morabito, K.M., and Graham, B.S. (2014). Quantitative and qualitative deficits in neonatal lung-migratory dendritic cells impact the generation of the CD8+ T cell response. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003934"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.4049\/jimmunol.179.3.1648","article-title":"Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC\/CCL17","volume":"179","author":"Monick","year":"2007","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ajpath.2011.03.003","article-title":"IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease","volume":"179","author":"Mukherjee","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8790","DOI":"10.1128\/JVI.00796-10","article-title":"CD25+ natural regulatory T cells are critical in limiting innate and adaptive immunity and resolving disease following respiratory syncytial virus infection","volume":"84","author":"Lee","year":"2010","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000355303","article-title":"Regulatory T cells and the immune aging process: A mini-review","volume":"60","author":"Jagger","year":"2014","journal-title":"Gerontology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jung, H.E., Kim, T.H., and Lee, H.K. (2020). Contribution of dendritic cells in protective immunity against respiratory syncytial virus infection. Viruses, 12.","DOI":"10.3390\/v12010102"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, D., Yang, J., Zhao, Y., Shan, J., Wang, L., Yang, G., He, S., and Li, E. (2022). RSV Infection in Neonatal Mice Induces Pulmonary Eosinophilia Responsible for Asthmatic Reaction. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.817113"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12191","DOI":"10.1128\/JVI.01604-08","article-title":"The secreted form of respiratory syncytial virus G glycoprotein helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy and through effects on Fc receptor-bearing leukocytes","volume":"82","author":"Bukreyev","year":"2008","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1189\/jlb.0412195","article-title":"Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration","volume":"94","author":"Jang","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309ra162","DOI":"10.1126\/scitranslmed.aac4241","article-title":"Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera","volume":"7","author":"Ngwuta","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1073\/pnas.1115941109","article-title":"Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention","volume":"109","author":"Magro","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1093\/infdis\/jiz390","article-title":"Safety and Immunogenicity of a Respiratory Syncytial Virus Fusion (F) Protein Nanoparticle Vaccine in Healthy Third-Trimester Pregnant Women and Their Infants","volume":"220","author":"Swamy","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1093\/infdis\/jiu316","article-title":"Respiratory syncytial virus transplacental antibody transfer and kinetics in mother\u2013infant pairs in Bangladesh","volume":"210","author":"Chu","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_52","first-page":"59","article-title":"Breast milk prefusion F immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness","volume":"219","author":"Mazur","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/viro.2001.1138","article-title":"Contribution of the respiratory syncytial virus G glycoprotein and its secreted and membrane-bound forms to virus replication in vitro and in vivo","volume":"289","author":"Teng","year":"2001","journal-title":"Virology"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Efstathiou, C., Zhang, Y., Kandwal, S., Fayne, D., Molloy, E.J., and Stevenson, N.J. (2024). Respiratory syncytial virus NS1 inhibits anti-viral Interferon-\u03b1-induced JAK\/STAT signaling, by limiting the nuclear translocation of STAT1. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1395809"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1189\/jlb.0313180","article-title":"Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection","volume":"95","author":"Wu","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"154481","DOI":"10.1016\/j.cyto.2018.07.012","article-title":"Cytokines and CD8 T cell immunity during respiratory syncytial virus infection","volume":"133","author":"Schmidt","year":"2020","journal-title":"Cytokine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1743-422X-2-46","article-title":"Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: An experimental murine model","volume":"2","author":"Olsen","year":"2005","journal-title":"Virol. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10224","DOI":"10.1038\/ncomms10224","article-title":"RSV-specific airway resident memory CD8\u207a T cells and differential disease severity after experimental human infection","volume":"6","author":"Jozwik","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1086\/657158","article-title":"Circulating antibody-secreting cells during acute respiratory syncytial virus infection in adults","volume":"202","author":"Lee","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/0300985814520639","article-title":"The relationship between respiratory syncytial virus and asthma","volume":"52","author":"Knudson","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/90675","article-title":"CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein","volume":"2","author":"Tripp","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","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":"ref_64","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.jaci.2015.06.034","article-title":"Neutrophils in respiratory syncytial virus infection: A target for asthma prevention","volume":"136","author":"Geerdink","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ouyang, Y., Liao, H., Hu, Y., Luo, K., Hu, S., and Zhu, H. (2022). Innate Immune Evasion by Human Respiratory Syncytial Virus. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.865592"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e2020587118","DOI":"10.1073\/pnas.2020587118","article-title":"Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2","volume":"118","author":"Pei","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1128\/JVI.02434-08","article-title":"Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I","volume":"83","author":"Ling","year":"2009","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"da Silva, R.P., Thom\u00e9, B.L., and da Souza, A.P.D. (2023). Exploring the Immune Response against RSV and SARS-CoV-2 Infection in Children. Biology, 12.","DOI":"10.3390\/biology12091223"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rivas-Fuentes, S., Salgado-Aguayo, A., Santos-Mendoza, T., and Sevilla-Reyes, E. (2024). The Role of the CX3CR1-CX3CL1 Axis in Respiratory Syncytial Virus Infection and the Triggered Immune Response. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202407.0855.v1"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Anderson, J., Do, L.A.H., van Kasteren, P.B., and Licciardi, P.V. (2024). The role of respiratory syncytial virus G protein in immune cell infection and pathogenesis. EBioMedicine, 107.","DOI":"10.1016\/j.ebiom.2024.105318"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Tognarelli, E.I., Bueno, S.M., and Gonz\u00e1lez, P.A. (2019). Immune-Modulation by the Human Respiratory Syncytial Virus: Focus on Dendritic Cells. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00810"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"13466","DOI":"10.1128\/JVI.01741-13","article-title":"Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial and immune cell responses","volume":"87","author":"Chirkova","year":"2013","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2217\/fvl.11.62","article-title":"Central role of dendritic cells in shaping the adaptive immune response during respiratory syncytial virus infection","volume":"6","author":"McDermott","year":"2011","journal-title":"Future Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/infdis\/jiq020","article-title":"RSV-induced bronchial epithelial cell PD-L1 expression inhibits CD8+ T cell nonspecific antiviral activity","volume":"203","author":"Telcian","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"617","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":"ref_76","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.2174\/092986712799828346","article-title":"Inflammatory responses to respiratory syncytial virus (RSV) infection and the development of immunomodulatory pharmacotherapeutics","volume":"19","author":"Rosenberg","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/modpathol.3800725","article-title":"The histopathology of fatal untreated human respiratory syncytial virus infection","volume":"20","author":"Johnson","year":"2007","journal-title":"Mod. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1600-065X.2010.00972.x","article-title":"Biological challenges and technological opportunities for respiratory syncytial virus vaccine development","volume":"239","author":"Graham","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1164\/ajrccm.161.5.9906076","article-title":"Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7","volume":"161","author":"Sigurs","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"977","DOI":"10.2353\/ajpath.2006.051055","article-title":"Differential immune responses and pulmonary pathophysiology are induced by two different strains of respiratory syncytial virus","volume":"169","author":"Lukacs","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nri3739","article-title":"The role of airway epithelial cells and innate immune cells in chronic respiratory disease","volume":"14","author":"Holtzman","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1111\/jpc.16197","article-title":"Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions","volume":"58","author":"Binns","year":"2022","journal-title":"J. Paediatr. Child Health"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jaci.2023.08.009","article-title":"Progress in understanding whether respiratory syncytial virus infection in infancy causes asthma in childhood","volume":"152","author":"Hasegawa","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1189\/jlb.4A1216-536R","article-title":"IL-4R\u03b1 on dendritic cells in neonates and Th2 immunopathology in respiratory syncytial virus infection","volume":"102","author":"Shrestha","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8734504","DOI":"10.1155\/2017\/8734504","article-title":"Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?","volume":"2017","author":"Drajac","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Saghafian-Hedengren, S., Sverremark-Ekstr\u00f6m, E., and Nilsson, A. (2021). T Cell Subsets During Early Life and Their Implication in the Treatment of Childhood Acute Lymphoblastic Leukemia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.582539"},{"key":"ref_87","unstructured":"Erickson, E.N., Bhakta, R.T., Tristram, D., and Mendez, M.D. (2025, January 12). Pediatric Bronchiolitis, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK519506\/."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/ni.2588","article-title":"Understanding immunosenescence to improve responses to vaccines","volume":"14","author":"Goronzy","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nri3547","article-title":"Age-dependent dysregulation of innate immunity","volume":"13","author":"Shaw","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.yfpn.2022.11.004","article-title":"Immunosenescence and Infectious Disease Risk Among Aging Adults: Management Strategies for FNPs to Identify Those at Greatest Risk","volume":"5","author":"Gray","year":"2023","journal-title":"Adv. Fam. Pract. Nurs."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"230266","DOI":"10.1183\/16000617.0266-2023","article-title":"Diverging patterns in innate immunity against respiratory viruses during a lifetime: Lessons from the young and the old","volume":"33","author":"Smits","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cyto.2010.09.011","article-title":"The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma","volume":"53","author":"Zeng","year":"2011","journal-title":"Cytokine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1006\/clim.2002.5248","article-title":"Chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis","volume":"104","author":"Noah","year":"2002","journal-title":"Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/infdis\/jiac404","article-title":"Type III Interferons, Viral Loads, Age, and Disease Severity in Young Children with Respiratory Syncytial Virus Infection","volume":"227","author":"Taveras","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zhang, G., Zhao, B., and Liu, J. (2024). The Development of Animal Models for Respiratory Syncytial Virus (RSV) Infection and Enhanced RSV Disease. Viruses, 16.","DOI":"10.3390\/v16111701"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Bohmwald, K., G\u00e1lvez, N.M.S., Canedo-Marroqu\u00edn, G., Pizarro-Ortega, M.S., Andrade-Parra, C., G\u00f3mez-Santander, F., and Kalergis, A.M. (2019). Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00452"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.4049\/jimmunol.166.5.3542","article-title":"IL-13-induced airway hyperreactivity during respiratory syncytial virus infection is STAT6 dependent","volume":"166","author":"Tekkanat","year":"2001","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1136\/thoraxjnl-2012-202404","article-title":"IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation","volume":"68","author":"Newcomb","year":"2013","journal-title":"Thorax"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1164\/rccm.200406-730OC","article-title":"Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13","volume":"171","author":"Sigurs","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1067\/S0022-3476(03)00454-2","article-title":"Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease","volume":"143","author":"Feltes","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1913556","article-title":"Single-dose nirsevimab for prevention of RSV in preterm infants","volume":"383","author":"Griffin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(10)60206-1","article-title":"Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis","volume":"375","author":"Nair","year":"2010","journal-title":"Lancet"},{"key":"ref_103","first-page":"S26","article-title":"Immunoprophylaxis of respiratory syncytial virus: Global experience","volume":"3","year":"2002","journal-title":"Respir. Res."},{"key":"ref_104","unstructured":"American Academy of Pediatrics Committee on Infectious Diseases, and American Academy of Pediatrics Bronchiolitis Guidelines Committee (2014). Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics, 134, e620\u2013e638."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e20184064","DOI":"10.1542\/peds.2018-4064","article-title":"Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus: A Systematic Review","volume":"143","author":"Mac","year":"2019","journal-title":"Pediatrics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1056\/NEJMoa2110275","article-title":"Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants","volume":"386","author":"Hammitt","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2352-4642(22)00321-2","article-title":"Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: A pooled analysis of randomised controlled trials","volume":"7","author":"Madhi","year":"2023","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa2309189","article-title":"Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants","volume":"389","author":"Drysdale","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_109","unstructured":"Centers for Disease Control and Prevention (CDC) (2023). Early estimates of nirsevimab immunoprophylaxis effectiveness in preventing RSV-associated hospitalizations among infants\u2014United States, October 2022\u2013February 2023. Morb. Mortal. Wkly. Rep., 72, 225\u2013229."},{"key":"ref_110","first-page":"CD001266","article-title":"Bronchodilators for bronchiolitis","volume":"2014","author":"Gadomski","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1001\/archpediatrics.2011.1669","article-title":"Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis","volume":"166","author":"Mansbach","year":"2012","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e647","DOI":"10.1093\/infdis\/jiae081","article-title":"Safety and immunogenicity of an mRNA-based RSV vaccine including a 12-month booster in a phase 1 clinical trial in healthy older adults","volume":"230","author":"Shaw","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1476-5381.2010.01199.x","article-title":"Glucocorticosteroids: Current and future directions","volume":"163","author":"Barnes","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_114","first-page":"CD004878","article-title":"Glucocorticoids for acute viral bronchiolitis in infants and young children","volume":"2013","author":"Fernandes","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/j.1651-2227.2005.tb02003.x","article-title":"Dexamethasone inhalations in RSV bronchiolitis: A double-blind, placebo-controlled study","volume":"94","author":"Bentur","year":"2005","journal-title":"Acta Paediatr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.anai.2023.01.010","article-title":"Steroid-induced secondary immune deficiency","volume":"130","author":"Mustafa","year":"2023","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.4049\/jimmunol.147.12.4307","article-title":"Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages","volume":"147","author":"Becker","year":"1991","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3892\/etm.2022.11660","article-title":"Factors predicting poor outcomes of patients treated with tocilizumab for COVID-19-associated pneumonia: A retrospective study","volume":"24","author":"Georgakopoulou","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/jcph.1693","article-title":"A comprehensive review of tocilizumab in COVID-19 acute respiratory distress syndrome","volume":"60","author":"Khiali","year":"2020","journal-title":"J. Clin. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Tanaka, T., Narazaki, M., and Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a016295"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1136\/adc.88.10.922","article-title":"Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis","volume":"88","author":"McNamara","year":"2003","journal-title":"Arch. Dis. Child."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT signaling as a target for inflammatory and autoimmune diseases: Current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cytogfr.2016.05.002","article-title":"A gradient of glucocorticoid sensitivity among helper T cell cytokines","volume":"31","author":"Banuelos","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11926-018-0792-7","article-title":"JAK Inhibitors in Rheumatology: Implications for Paediatric Syndromes?","volume":"20","author":"Kerrigan","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"94","DOI":"10.14740\/jmc3629","article-title":"A novel report on the compassionate use of baricitinib in treating a pediatric patient with severe symptoms of COVID-19 infection","volume":"12","author":"Atemnkeng","year":"2021","journal-title":"J. Med. Cases"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Yue, Z., Zhang, X., Gu, Y., Liu, Y., Lan, L.M., Liu, Y., Li, Y., Yang, G., Wan, P., and Chen, X. (2024). Regulation and functions of the NLRP3 inflammasome in RNA virus infection. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1309128"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e70003","DOI":"10.1111\/imr.70003","article-title":"Inflammasome Activation by RNA Respiratory Viruses: Mechanisms, Viral Manipulation, and Therapeutic Insights","volume":"330","author":"Rodrigues","year":"2025","journal-title":"Immunol. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Zeng, J., Xie, X., Feng, X.L., Xu, L., Han, J.B., Yu, D., Zou, Q.C., Liu, Q., Li, X., and Ma, G. (2022). Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice. EBioMedicine, 75.","DOI":"10.1016\/j.ebiom.2021.103803"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1016\/j.apsb.2025.02.015","article-title":"Advances in development of antiviral strategies against respiratory syncytial virus","volume":"15","author":"Yang","year":"2025","journal-title":"Acta Pharm. Sinica. B"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1401184","article-title":"Oral GS-5806 activity in a respiratory syncytial virus challenge study","volume":"371","author":"DeVincenzo","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1093\/cid\/ciz1167","article-title":"A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract","volume":"71","author":"Marty","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1056\/NEJMoa1413275","article-title":"Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study","volume":"373","author":"DeVincenzo","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa2313551","article-title":"Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection","volume":"391","author":"Zhao","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S2352-4642(25)00067-7","article-title":"Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: Findings from a phase 3 randomised trial with 24-month follow-up","volume":"9","author":"Zhang","year":"2025","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41392-024-01858-5","article-title":"Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein","volume":"9","author":"Yang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1128\/JVI.02417-15","article-title":"The Interferon Type I\/III Response to Respiratory Syncytial Virus Infection in Airway Epithelial Cells Can Be Attenuated or Amplified by Antiviral Treatment","volume":"90","author":"McCutcheon","year":"2015","journal-title":"J. Virol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Funchal, G.A., Jaeger, N., Czepielewski, R.S., Machado, M.S., Muraro, S.P., Stein, R.T., Bonorino, C.B., and Porto, B.N. (2015). Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124082"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ismej.2015.99","article-title":"Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients","volume":"10","author":"Huijskens","year":"2016","journal-title":"ISME J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.jaci.2021.12.758","article-title":"Role of nasal microbiota and host response in infants with respiratory syncytial virus infection: Causal questions about respiratory outcomes","volume":"149","author":"Hasegawa","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.12688\/f1000research.9637.1","article-title":"Respiratory syncytial virus infection: An innate perspective","volume":"5","author":"Johansson","year":"2016","journal-title":"F1000Research"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"van Erp, E.A., Luytjes, W., Ferwerda, G., and van Kasteren, P.B. (2019). Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00548"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41577-022-00734-z","article-title":"Host-directed immunotherapy of viral and bacterial infections: Past, present and future","volume":"23","author":"Wallis","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.it.2015.09.009","article-title":"Impact of Early-Life Exposures on Immune Maturation and Susceptibility to Disease","volume":"36","author":"Gollwitzer","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Norlander, A.E., and Peebles, R.S. (2020). Innate Type 2 Responses to Respiratory Syncytial Virus Infection. Viruses, 12.","DOI":"10.3390\/v12050521"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1016\/j.vaccine.2011.04.077","article-title":"Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults","volume":"29","author":"Yao","year":"2011","journal-title":"Vaccine"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2165\/00002512-200522070-00004","article-title":"Respiratory syncytial virus infection in elderly adults","volume":"22","author":"Falsey","year":"2005","journal-title":"Drugs Aging"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1874285801408010071","article-title":"Respiratory Syncytial Virus Infection in High-risk Infants\u2014An Update on Palivizumab Prophylaxis","volume":"8","author":"Resch","year":"2014","journal-title":"Open Microbiol. J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1067\/mpd.2000.110531","article-title":"Rates of hospitalization for respiratory syncytial virus infection among children in medicaid","volume":"137","author":"Boyce","year":"2000","journal-title":"J. Pediatr."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"7394","DOI":"10.1016\/j.vaccine.2017.09.092","article-title":"Respiratory syncytial virus vaccine research and development: World Health Organization technological roadmap and preferred product characteristics","volume":"37","author":"Vekemans","year":"2019","journal-title":"Vaccine"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"B209","DOI":"10.1016\/j.vaccine.2012.11.106","article-title":"Strategic priorities for respiratory syncytial virus (RSV) vaccine development","volume":"31","author":"Anderson","year":"2013","journal-title":"Vaccine"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMoa2216480","article-title":"Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants","volume":"388","author":"Kampmann","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1016\/S1473-3099(18)30292-5","article-title":"The respiratory syncytial virus vaccine landscape: Lessons from the graveyard and promising candidates","volume":"18","author":"Mazur","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines\u2014A new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Georgakopoulou, V.E., Papalexis, P., and Trakas, N. (2024). Nanotechnology-based approaches for targeted drug delivery for the treatment of respiratory tract infections. J. Biol. Methods, 11.","DOI":"10.14440\/jbm.2024.0065"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Boyoglu-Barnum, S., Ellis, D., Gillespie, R.A., Hutchinson, G.B., Park, Y.J., Moin, S.M., Acton, O., Ravichandran, R., Murphy, M., and Pettie, D. (2020). Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines. bioRxiv.","DOI":"10.1101\/2020.05.30.125179"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Mul\u00e8, M.P., Martins, A.J., Cheung, F., Farmer, R., Sellers, B., Quiel, J.A., Jain, A., Kotliarov, Y., Bansal, N., and Chen, J. (2023). Multiscale integration of human and single-cell variations reveals unadjuvanted vaccine high responders are naturally adjuvanted. medRxiv.","DOI":"10.1101\/2023.03.20.23287474"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1152\/physrev.00030.2019","article-title":"Impact of respiratory syncytial virus infection on host functions: Implications for antiviral strategies","volume":"100","author":"Hu","year":"2020","journal-title":"Physiol. Rev."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1876\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:15Z","timestamp":1760034315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":158,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["microorganisms13081876"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13081876","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}