{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(12)"],"submitter":["Bakkers MJG"],"pubmed_abstract":["Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and older people. Current RSV subunit vaccines are based on a fusion protein that is stabilized in the prefusion conformation and linked to a heterologous foldon trimerization domain to obtain a prefusion F (preF) trimer. Here we show that current RSV vaccines induce undesirable anti-foldon antibodies in non-human primates, mice and humans. To overcome this, we designed a foldon-free RSV preF trimer by elucidating the structural basis of trimerization-induced preF destabilization through molecular dynamics simulations and by introducing amino acid substitutions that negate hotspots of charge repulsion. The highly stable prefusion conformation was validated using antigenic and cryo-electron microscop"],"journal":["Nature microbiology"],"pagination":["3254-3267"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11602707"],"repository":["biostudies-literature"],"pubmed_title":["A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses."],"pmcid":["PMC11602707"],"pubmed_authors":["van der Fits L","Le L","Vaneman J","Thoma A","Zahn R","van Overveld D","Tettero L","Koornneef A","Bakkers MJG","Cox F","Juraszek J","van den Hoogen W","Langedijk JPM","Voorzaat R","Yu X"],"additional_accession":[]},"is_claimable":false,"name":"A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses.","description":"Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and older people. Current RSV subunit vaccines are based on a fusion protein that is stabilized in the prefusion conformation and linked to a heterologous foldon trimerization domain to obtain a prefusion F (preF) trimer. Here we show that current RSV vaccines induce undesirable anti-foldon antibodies in non-human primates, mice and humans. To overcome this, we designed a foldon-free RSV preF trimer by elucidating the structural basis of trimerization-induced preF destabilization through molecular dynamics simulations and by introducing amino acid substitutions that negate hotspots of charge repulsion. The highly stable prefusion conformation was validated using antigenic and cryo-electron microscop","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-02T06:24:44.577Z","creation":"2025-04-04T09:59:09.838Z"},"accession":"S-EPMC11602707","cross_references":{"pubmed":["39567664"],"doi":["10.1038/s41564-024-01860-1"]}}