biostudies-literatureHu ZNational Natural Science Foundation of ChinaNational Key Research and Development Program of Chinae0090325https://www.ebi.ac.uk/biostudies/studies/S-EPMC12455995biostudies-literatureUnknown99(9)Respiratory syncytial virus (RSV) is a global public health concern. Currently, RSV vaccines are approved only for use in older adults, while preventing the disease in infants and children, as well as ensuring vaccine durability, remains a significant challenge. The pre-fusion conformation of the RSV fusion (F) glycoprotein is a primary target for vaccine development, as it elicits significantly higher neutralizing antibody titers than the post-fusion form. Here, we conjugated either the first-generation RSV pre-fusion F antigen, DS-Cav1, or the second-generation antigen, Sc9-10, to a computationally designed nanoparticle platform, NPM, via a Catcher/Tag system. Conjugating RSV pre-fusion F to NPM significantly enhanced immunogenicity, stability, and bioactivity compared to display on the Journal of virologyNanoparticle vaccine based on the pre-fusion F glycoprotein of respiratory syncytial virus elicits robust protective immune responses.PMC12455995820250012024YFA09200012024YFA092000282495203Liu JYu RHu ZGuo YLiu SZhang SZou YWei PDing YYao YRen LWei RZhao DWang YZhang CZhao JJin JMo XZhou PChen HZhou YZhuang ZZang NDeng CLi YPeng GTian SJing CFu MLiu EfalseNanoparticle vaccine based on the pre-fusion F glycoprotein of respiratory syncytial virus elicits robust protective immune responses.Respiratory syncytial virus (RSV) is a global public health concern. Currently, RSV vaccines are approved only for use in older adults, while preventing the disease in infants and children, as well as ensuring vaccine durability, remains a significant challenge. The pre-fusion conformation of the RSV fusion (F) glycoprotein is a primary target for vaccine development, as it elicits significantly higher neutralizing antibody titers than the post-fusion form. Here, we conjugated either the first-generation RSV pre-fusion F antigen, DS-Cav1, or the second-generation antigen, Sc9-10, to a computationally designed nanoparticle platform, NPM, via a Catcher/Tag system. Conjugating RSV pre-fusion F to NPM significantly enhanced immunogenicity, stability, and bioactivity compared to display on the 2025-01-01T00:00:00Z2025 Sep2026-07-15T05:46:52.169Z2026-06-29T03:19:37.693ZS-EPMC124559954085649110.1128/jvi.00903-25