Evidence map›Paper›PMID 38177144›Full record

ArticleNature communications2024

Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.

Jason Gorman, Crystal Sao-Fong Cheung, Zhijian Duan, Li Ou, Maple Wang, Xuejun Chen, Cheng Cheng, Andrea Biju, Yaping Sun, Pengfei Wang and 27 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  9. Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
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  11. Review
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  18. Article
  19. Strategies of rational and structure-driven vaccine design for Arenaviruses.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors at 3 institutions in 1 country.

Jason GormanVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0002-3775-6560
Crystal Sao-Fong Cheung *Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Zhijian Duan *NCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Li Ou *Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Maple Wang *Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Xuejun ChenVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0001-9192-0440
Cheng ChengVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Andrea BijuVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Yaping SunNCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Pengfei WangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.ORCID 0000-0003-2454-7652
Yongping YangVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Baoshan ZhangVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Jeffrey C BoyingtonVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Tatsiana BylundVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Sam CharafVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Steven J ChenVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Haijuan DuVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Amy R HenryVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Tracy LiuVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Edward K SarfoVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0001-9015-3446
Chaim A SchrammVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0002-2562-603X
Chen-Hsiang ShenVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Tyler StephensElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
I-Ting TengVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
John-Paul ToddVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Yaroslav TsybovskyElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.ORCID 0000-0002-2159-5248
Raffaello VerardiVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0002-2613-1223
Danyi WangVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0009-0008-0820-7037
Shuishu WangVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0002-0865-4522
Zhantong WangVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Cheng-Yan ZhengVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Tongqing ZhouVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0002-3935-4637
Daniel C DouekVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID 0000-0001-5575-8634
John R MascolaVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA.
David D HoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA. dh2994@cumc.columbia.edu.
Mitchell HoNCI Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. homi@mail.nih.gov.ORCID 0000-0002-9152-5405
Peter D KwongVaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA. pdkwong@nih.gov.ORCID 0000-0003-3560-232X
National Institutes of Health · USAaron Diamond AIDS Research Center · USLeidos (United States) · US

Funding

Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6M
Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
Mechanisms Of Humoral EvasionZIAAI005023 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$18.6M
PREMISE: Pandemic Response Repository through Microbial and Immune Surveillance and EpidemiologyZIAAI005166 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2022 to 2025
$17.8M
HIV/AIDS Vaccine and Antibody DevelopmentZICAI005002 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHENG, CHENG · 2019 to 2025
$17.6M
TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
Innate and Adaptive Immune Responses in SARS-CoV-2 infection (COVID-19)ZIAAI005151 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2020 to 2025
$6.8M
Antibody Engineering ProgramZICBC011891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2019 to 2025
$4.5M
Design of Antigenically-Specific Probes for Sera Analysis and MAb IsolationZICAI005111 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2010 to 2025
$4.3M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA AI005022Intramural NIH HHS ZIA AI005024NCI NIH HHS HHSN261200800001ENIGMS NIH HHS P41 GM103310
6 · The paper itself

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.

Indexed as

Lassa FeverSingle-Domain AntibodiesAnimalsAntibodies, NeutralizingAntibodies, ViralGuinea PigsLassa virusAntibodies, NeutralizingAntibodies, ViralSingle-Domain Antibodies

Identifiers

PMID38177144
PMCPMC10767048
OpenAlexW4390579413

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.