biostudies-literatureWidge ATIntramural NIH HHSNIAID NIH HHSeade4790https://www.ebi.ac.uk/biostudies/studies/S-EPMC10619166biostudies-literatureUnknown15(692)Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once (<i>n</i> = 5) or 60 μg of H1ssF twice (<i>n</i> = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participanScience translational medicineAn influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.PMC1061916675N93021C0001475N93019C00051Z99 AI999999P01 AI097092R01 AI145870Telscher SLeach KPatel ADropulic LKCooper JCunningham JDobrescu GCastro MStrom LWang XEHatcher CVRC 321 study teamArthur AHolland-Linn JCostner PGollapudi DGordon IJAdams WCHong JSCasazza JBanappagari SCarlton KStein JALarkin BOla AOChen GLYang RSWidge ATWycuff DBeck AMcDermott ABKueltzo LGillespie RALedgerwood JELawlor HRothwell RSBender MWilliams PLiang CJVickery KNovik LYi YLee JZhao WNarpala SRZhao ZGaudinski MRBerkowitz NMKoup RAGowetski DCrank MCBurch EHofstetter ARRequilman LHicks RChintamani MLiu JACase CLMascola JRUpadhyay SPittman IApte PLei PSitar SLambert NFreyn AWBahorich JYamshchikov GTrofymenko OAndrews SFCoates EESaunders JDemirji JKanekiyo MShaddeau APlummer SParker KChaudhuri RCreanga ARosales EDinh TSerebryannyy LAWu RGottumukkala RWang XHorwitz JMendoza FGoh AAwan SFLe LYang JGall JGO'Connell SAlbright GNachbagauer REvans CManceva SLi YYang YJones JRagunathan RHendel CSEshun AMIvleva VHouser KVBurgos Florez MCWhalen WVasilenko OVazquez SRosado VCLaPanse APalese PCaringal ATNguyen TCarvalho JHolman LAGraham BSRomaine LAnderson MShadrick WMisasi JLin BCSchneck NCartagena CTGraves CfalseAn influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once (<i>n</i> = 5) or 60 μg of H1ssF twice (<i>n</i> = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participan2023-01-01T00:00:00Z2023 Apr2026-05-29T07:14:12.337Z2025-04-04T14:35:58.886ZS-EPMC106191663707512910.1126/scitranslmed.ade4790