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Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.
Gorman, Jason; Cheung, Crystal Sao-Fong; Duan, Zhijian; Ou, Li; Wang, Maple; Chen, Xuejun; Cheng, Cheng; Biju, Andrea; Sun, Yaping; Wang, Pengfei; Yang, Yongping; Zhang, Baoshan; Boyington, Jeffrey C; Bylund, Tatsiana; Charaf, Sam; Chen, Steven J; Du, Haijuan; Henry, Amy R; Liu, Tracy; Sarfo, Edward K; Schramm, Chaim A; Shen, Chen-Hsiang; Stephens, Tyler; Teng, I-Ting; Todd, John-Paul; Tsybovsky, Yaroslav; Verardi, Raffaello; Wang, Danyi; Wang, Shuishu; Wang, Zhantong; Zheng, Cheng-Yan; Zhou, Tongqing; Douek, Daniel C; Mascola, John R; Ho, David D; Ho, Mitchell; Kwong, Peter D.
Afiliação
  • Gorman J; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Cheung CS; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Duan Z; NCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Ou L; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang M; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
  • Chen X; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Cheng C; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Biju A; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Sun Y; NCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang P; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
  • Yang Y; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Zhang B; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Boyington JC; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Bylund T; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Charaf S; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Chen SJ; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Du H; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Henry AR; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Liu T; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Sarfo EK; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Schramm CA; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Shen CH; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Stephens T; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
  • Teng IT; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Todd JP; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Tsybovsky Y; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
  • Verardi R; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang D; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang S; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Wang Z; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Zheng CY; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Zhou T; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Douek DC; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Mascola JR; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA. dh2994@cumc.columbia.edu.
  • Ho M; NCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. homi@mail.nih.gov.
  • Kwong PD; Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA. pdkwong@nih.gov.
Nat Commun ; 15(1): 285, 2024 Jan 04.
Article em En | MEDLINE | ID: mdl-38177144
ABSTRACT
Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos de Domínio Único / Febre Lassa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos de Domínio Único / Febre Lassa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article