{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:49:27Z","timestamp":1785408567312,"version":"3.56.0"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007613","name":"Majmaah University","doi-asserted-by":"crossref","award":["R-2026-249"],"award-info":[{"award-number":["R-2026-249"]}],"id":[{"id":"10.13039\/501100007613","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R-2026-249"],"award-info":[{"award-number":["R-2026-249"]}],"id":[{"id":"https:\/\/ror.org\/01mcrnj60","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Respiratory syncytial virus (RSV) is considered the leading causative agent of acute lower respiratory infections in infants and young children worldwide, which makes it a major contributor to pediatric morbidity and mortality. Infants are especially susceptible to severe disease in early life, which underlines the urgent need for developing effective immunization strategies against this virus. However, the development of vaccines against RSV has long been associated with significant challenges. For example, initial attempts, especially those involving formalin-inactivated RSV, resulted in vaccine-enhanced respiratory disease upon subsequent infection, which set a significant safety obstacle for future vaccine candidates. Other challenges facing vaccine development against RSV include the short-lived immunity induced by natural infection, lack of clear correlates of immunity, and immune naivety in infants. Recent breakthroughs in structural virology and immunology have provided insights into protective immunity against RSV, especially regarding neutralizing antibodies that recognize the virus in its prefusion conformation of the viral F protein. Among promising vaccine candidates, intranasal live-attenuated vaccines have emerged as especially promising for infant immunization, especially considering their close mimicry of natural infection that can elicit systemic as well as mucosal immunity in the respiratory tract. A newly emerging approach for live-attenuated virus vaccine development is codon-pair deoptimization (CPD), which is based on synthetic recoding that reduces viral replicative capacity while maintaining intact protein sequences and structure. The preclinical results of CPD-based RSV candidates have provided evidence of such vaccines\u2019 ability to elicit robust immunity while maintaining favorable safety profiles. This review addresses the major challenges associated with the development of effective RSV vaccines for infant immunization, with particular emphasis on lessons learned from previous vaccine failures and recent advances in RSV vaccine development, particularly CPD-based attenuation strategies.<\/jats:p>","DOI":"10.3390\/ijms27125231","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:33:44Z","timestamp":1781073224000},"page":"5231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Codon-Pair Deoptimized (CPD) Intranasal RSV Vaccines: A Novel Strategy for Infant Protection"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-7582","authenticated-orcid":false,"given":"Wael","family":"Alturaiki","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alturaiki, W., and Flanagan, B. (2025). Respiratory Syncytial Virus Induces B Cell Activating Factor (BAFF) in Airway Epithelium: A Potential Avenue for Mucosal Vaccine Development. Viruses, 17.","DOI":"10.3390\/v17070946"},{"key":"ref_2","unstructured":"WHO (2025, July 30). Respiratory Syncytial Virus (RSV). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/respiratory-syncytial-virus-(rsv)#:~:text=Scope%20of%20the%20problem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/oxfordjournals.aje.a120955","article-title":"Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine","volume":"89","author":"Kim","year":"1969","journal-title":"Am. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1513\/pats.200501-002AW","article-title":"Pathogenesis of respiratory syncytial virus infection in the murine model","volume":"2","author":"Peebles","year":"2005","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.coviro.2012.01.008","article-title":"Pathogenesis of respiratory syncytial virus","volume":"2","author":"Watkiss","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.4049\/jimmunol.179.8.5415","article-title":"CD8 T cells inhibit respiratory syncytial virus (RSV) vaccine-enhanced disease","volume":"179","author":"Olson","year":"2007","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7958","DOI":"10.4049\/jimmunol.181.11.7958","article-title":"The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia","volume":"181","author":"Olson","year":"2008","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Knudson, C.J., Hartwig, S.M., Meyerholz, D.K., and Varga, S.M. (2015). RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004757"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.coviro.2014.03.009","article-title":"Mucosal vaccines against respiratory syncytial virus","volume":"6","author":"Yang","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Malkin, E., Yogev, R., Abughali, N., Sliman, J., Wang, C.K., Zuo, F., Yang, C.-F., Eickhoff, M., Esser, M.T., and Tang, R.S. (2013). Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077104"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Soto, J.A., Stephens, L.M., Waldstein, K.A., Canedo-Marroqu\u00edn, G., Varga, S.M., and Kalergis, A.M. (2020). Current insights in the development of efficacious vaccines against RSV. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01507"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1164\/rccm.201810-1921OC","article-title":"Local and systemic immunity against respiratory syncytial virus induced by a novel intranasal vaccine. A randomized, double-blind, placebo-controlled clinical trial","volume":"200","author":"Ascough","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/mi.2016.48","article-title":"Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung","volume":"10","author":"Morabito","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11034","DOI":"10.1038\/s41598-018-29456-w","article-title":"Type I interferon potentiates IgA immunity to respiratory syncytial virus infection during infancy","volume":"8","author":"Hijano","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41541-019-0150-4","article-title":"Adenovectors encoding RSV-F protein induce durable and mucosal immunity in macaques after two intramuscular administrations","volume":"4","author":"Salisch","year":"2019","journal-title":"npj Vaccines"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Levy, M., Chen, J.W., Kaiser, J.A., Park, H.-S., Liu, X., Yang, L., Santos, C., Buchholz, U.J., and Le Nou\u00ebn, C. (2024). Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal and systemic immunity and protection against challenge virus replication in hamsters. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012198"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1016\/j.vaccine.2020.02.056","article-title":"A codon-pair deoptimized live-attenuated vaccine against respiratory syncytial virus is immunogenic and efficacious in non-human primates","volume":"38","author":"Mueller","year":"2020","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1099\/0022-1317-67-7-1247","article-title":"An RNA-dependent RNA polymerase associated with the filamentous nucleoproteins of rice stripe virus","volume":"67","author":"Toriyama","year":"1986","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhou, X., Jiang, M., Wang, F., Qian, Y., Song, Q., Sun, Y., Zhu, R., Wang, F., Qu, D., and Cao, L. (2023). Immune escaping of the novel genotypes of human respiratory syncytial virus based on gene sequence variation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1084139"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ke, Z., Dillard, R.S., Chirkova, T., Leon, F., Stobart, C.C., Hampton, C.M., Strauss, J.D., Rajan, D., Rostad, C.A., and Taylor, J.V. (2018). The morphology and assembly of respiratory syncytial virus revealed by cryo-electron tomography. Viruses, 10.","DOI":"10.3390\/v10080446"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1099\/jgv.0.000261","article-title":"Human respiratory syncytial virus non-structural protein NS1 modifies miR-24 expression via transforming growth factor-\u03b2","volume":"96","author":"Bakre","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.virusres.2011.09.020","article-title":"Progress in understanding and controlling respiratory syncytial virus: Still crazy after all these years","volume":"162","author":"Collins","year":"2011","journal-title":"Virus Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1039\/C6MB00122J","article-title":"Functional correlations of respiratory syncytial virus proteins to intrinsic disorder","volume":"12","author":"Whelan","year":"2016","journal-title":"Mol. Biosyst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41392-023-01602-5","article-title":"Cryo-EM structure of the nucleocapsid-like assembly of respiratory syncytial virus","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cao, D., Gao, Y., and Liang, B. (2021). Structural insights into the respiratory syncytial virus RNA synthesis complexes. Viruses, 13.","DOI":"10.3390\/v13050834"},{"key":"ref_26","first-page":"001095","article-title":"Genomic characterization of respiratory syncytial virus genotypes circulating in the paediatric population of Sydney, NSW, Australia","volume":"9","author":"Pangesti","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Blanchard, E.L., Braun, M.R., Lifland, A.W., Ludeke, B., Noton, S.L., Vanover, D., Zurla, C., Fearns, R., and Santangelo, P.J. (2020). Polymerase-tagged respiratory syncytial virus reveals a dynamic rearrangement of the ribonucleocapsid complex during infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008987"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Noton, S.L., Deflub\u00e9, L.R., Tremaglio, C.Z., and Fearns, R. (2012). The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002980"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cox, F., Saeland, E., Thoma, A., van den Hoogen, W., Tettero, L., Drijver, J., Vaneman, C., van Polanen, Y., Ritschel, T., and Bastian, A.R. (2023). RSV A2-based prefusion F vaccine candidates induce RSV A and RSV B cross binding and neutralizing antibodies and provide protection against RSV A and RSV B challenge in preclinical models. Vaccines, 11.","DOI":"10.3390\/vaccines11030672"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/QCO.0000000000000952","article-title":"The disease burden of respiratory syncytial virus in Infants","volume":"36","author":"Munro","year":"2023","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e02357-16","DOI":"10.1128\/JVI.02357-16","article-title":"Broadly Reactive Anti-Respiratory Syncytial Virus G Antibodies from Exposed Individuals Effectively Inhibit Infection of Primary Airway Epithelial Cells","volume":"91","author":"Cortjens","year":"2017","journal-title":"J. Virol."},{"key":"ref_32","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_33","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_34","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_35","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMoa2307079","article-title":"Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults","volume":"389","author":"Wilson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s41043-026-01270-5","article-title":"Maternal RSV immunization: Clinical efficacy, immunological mechanisms and public health implications for preventing infant lower respiratory tract infection","volume":"45","author":"Amin","year":"2026","journal-title":"J. Health Popul. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Principi, N., Perrone, S., and Esposito, S. (2025). Challenges and limitations of current RSV prevention strategies in infants and young children: A narrative review. Vaccines, 13.","DOI":"10.3390\/vaccines13070717"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhou, J., Zhou, Y., Luo, K., Liao, Q., Zheng, W., Gong, H., Shi, H., Zhao, S., Wang, K., and Qiu, Q. (2022). The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0\u201313 years of age: A longitudinal cohort study. BMC Med., 20.","DOI":"10.1186\/s12916-022-02604-w"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1016\/j.vaccine.2022.06.034","article-title":"Biological factors that may impair transplacental transfer of RSV antibodies: Implications for maternal immunization policy and research priorities for low-and middle-income countries","volume":"40","author":"Atwell","year":"2022","journal-title":"Vaccine"},{"key":"ref_40","first-page":"e68349","article-title":"Use of the Abrysvo Vaccine in Pregnancy to Prevent Respiratory Syncytial Virus in Infants: A Review","volume":"16","author":"Patel","year":"2024","journal-title":"Cureus"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1542\/peds.102.3.531","article-title":"Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants","volume":"102","author":"Group","year":"1998","journal-title":"Pediatrics"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1056\/NEJMoa2502984","article-title":"Clesrovimab for prevention of RSV disease in healthy infants","volume":"393","author":"Zar","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e70257","DOI":"10.1111\/pai.70257","article-title":"Prophylactic monoclonal antibodies against respiratory syncytial virus in early life: An in-depth review of mechanisms of action, failure factors, and future perspectives","volume":"36","author":"Bizot","year":"2025","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Esposito, S., Abu Raya, B., Baraldi, E., Flanagan, K., Martinon Torres, F., Tsolia, M., and Zielen, S. (2022). RSV prevention in all infants: Which is the most preferable strategy?. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.880368"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1080\/21645515.2017.1337614","article-title":"Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection","volume":"13","author":"Resch","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"e230023","DOI":"10.1001\/jamanetworkopen.2023.0023","article-title":"Monoclonal antibody for the prevention of respiratory syncytial virus in infants and children: A systematic review and network meta-analysis","volume":"6","author":"Sun","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ananworanich, J., and Heaton, P.M. (2021). Bringing preventive RSV monoclonal antibodies to infants in low-and middle-income countries: Challenges and opportunities. Vaccines, 9.","DOI":"10.3390\/vaccines9090961"},{"key":"ref_50","first-page":"q2852","article-title":"FDA pauses all infant RSV vaccine trials after rise in severe illnesses","volume":"387","author":"Mahase","year":"2024","journal-title":"BMJ Br. Med. J. (Online)"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1126\/science.1155761","article-title":"Virus attenuation by genome-scale changes in codon pair bias","volume":"320","author":"Coleman","year":"2008","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"116939","DOI":"10.5501\/wjv.v15.i1.116939","article-title":"Next-generation mucosal vaccines for respiratory viruses: Immunological correlates, platform design and clinical translation","volume":"15","author":"Younas","year":"2026","journal-title":"World J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41541-025-01280-0","article-title":"Advances and prospects of respiratory mucosal vaccines: Mechanisms, technologies, and clinical applications","volume":"10","author":"Li","year":"2025","journal-title":"npj Vaccines"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dotiwala, F., and Upadhyay, A.K. (2023). Next generation mucosal vaccine strategy for respiratory pathogens. Vaccines, 11.","DOI":"10.3390\/vaccines11101585"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Alturaiki, W. (2026). The Role of Lung Microbiota in Shaping Host Immunity and Mucosal Vaccine Responses. Vaccines, 14.","DOI":"10.3390\/vaccines14040355"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/infdis\/jiz408","article-title":"Safety and immunogenicity of the respiratory syncytial virus vaccine RSV\/\u0394NS2\/\u03941313\/I1314L in RSV-seronegative children","volume":"222","author":"Karron","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1016\/j.vaccine.2023.05.011","article-title":"Advances in intranasal vaccine delivery: A promising non-invasive route of immunization","volume":"41","author":"Kehagia","year":"2023","journal-title":"Vaccine"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Karron, R.A., Buchholz, U.J., and Collins, P.L. (2013). Live-attenuated respiratory syncytial virus vaccines. Challenges and Opportunities for Respiratory Syncytial Virus Vaccines, Springer.","DOI":"10.1007\/978-3-642-38919-1_13"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2165","DOI":"10.1016\/S2214-109X(25)00379-1","article-title":"The path to equitable respiratory syncytial virus prevention for infants: Challenges and opportunities for global implementation","volume":"13","author":"Shaaban","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"24541","DOI":"10.1039\/D5NR01452B","article-title":"An optimized intranasal LNP formulation for potent immune responses of mRNA-based RSV vaccines","volume":"17","author":"Li","year":"2025","journal-title":"Nanoscale"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1016\/j.vaccine.2016.03.109","article-title":"Advances in RSV vaccine research and development\u2013a global agenda","volume":"34","author":"Higgins","year":"2016","journal-title":"Vaccine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e747","DOI":"10.1016\/S1473-3099(24)00455-9","article-title":"The respiratory syncytial virus vaccine and monoclonal antibody landscape: The road to global access","volume":"24","author":"Terstappen","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/irv.12850","article-title":"The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review","volume":"15","author":"Shan","year":"2021","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Deng, L., Cao, H., Li, G., Zhou, K., Fu, Z., Zhong, J., Wang, Z., and Yang, X. (2025). Progress on respiratory syncytial virus vaccine development and evaluation methods. Vaccines, 13.","DOI":"10.3390\/vaccines13030304"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Anastassopoulou, C., Medi\u0107, S., Ferous, S., Boufidou, F., and Tsakris, A. (2025). Development, current status, and remaining challenges for respiratory syncytial virus vaccines. Vaccines, 13.","DOI":"10.3390\/vaccines13020097"},{"key":"ref_66","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_67","doi-asserted-by":"crossref","unstructured":"Biagi, C., Dondi, A., Scarpini, S., Rocca, A., Vandini, S., Poletti, G., and Lanari, M. (2020). Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines. Vaccines, 8.","DOI":"10.3390\/vaccines8040672"},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"uqaf003","DOI":"10.1093\/femsml\/uqaf003","article-title":"Respiratory syncytial virus: Health burden, disease prevention, and treatment\u2014Recent progress and lessons learned","volume":"6","year":"2025","journal-title":"Microlife"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Topalidou, X., Kalergis, A.M., and Papazisis, G. (2023). Respiratory syncytial virus vaccines: A review of the candidates and the approved vaccines. Pathogens, 12.","DOI":"10.3390\/pathogens12101259"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nbt.1636","article-title":"Live attenuated influenza virus vaccines by computer-aided rational design","volume":"28","author":"Mueller","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107586","DOI":"10.1016\/j.celrep.2020.107586","article-title":"Mechanism of Virus Attenuation by Codon Pair Deoptimization","volume":"31","author":"Groenke","year":"2020","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13169","DOI":"10.1073\/pnas.1411290111","article-title":"Attenuation of human respiratory syncytial virus by genome-scale codon-pair deoptimization","volume":"111","author":"Brock","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1016\/S2666-5247(23)00195-7","article-title":"First RSV vaccine approvals","volume":"4","author":"Venkatesan","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.vaccine.2019.10.048","article-title":"Summary of the Vaccines and Related Biological Products Advisory Committee meeting held to consider evaluation of vaccine candidates for the prevention of respiratory syncytial virus disease in RSV-na\u00efve infants","volume":"38","author":"Browne","year":"2020","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cytogfr.2022.10.001","article-title":"Development of mRNA vaccines against respiratory syncytial virus (RSV)","volume":"68","author":"Qiu","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eade6422","DOI":"10.1126\/scitranslmed.ade6422","article-title":"Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine","volume":"15","author":"Che","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000536031","article-title":"Respiratory syncytial virus maternal vaccination in infants below 6 months of age: Meta-analysis of safety, immunogenicity, and efficacy","volume":"121","author":"Mapindra","year":"2024","journal-title":"Neonatology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1093\/cid\/ciaf033","article-title":"Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine","volume":"82","author":"Banooni","year":"2025","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S1473-3099(22)00291-2","article-title":"Respiratory syncytial virus prevention within reach: The vaccine and monoclonal antibody landscape","volume":"23","author":"Mazur","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/infdis\/jiad271","article-title":"Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6\u20137 months of age: A phase 1\/2 randomized trial","volume":"229","author":"Norero","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S1473-3099(25)00231-2","article-title":"Maternal vaccination to prevent severe RSV disease in infants","volume":"25","author":"Zar","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_83","unstructured":"(2025, July 30). Codagenix Receives FDA Fast Track Designation for Live-Attenuated, Intranasal RSV Vaccine Candidate CodaVax\u2122-RSV. Available online: https:\/\/codagenix.com\/codagenix-receives-fda-fast-track-designation-for-live-attenuated-intranasal-rsv-vaccine-candidate-codavax-rsv\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:22:32Z","timestamp":1781324552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":83,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125231"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125231","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}