Evidence map›Paper›PMID 32780770›Full record

ArticlePLoS pathogens2020

Structural and functional evaluation of de novo-designed, two-component nanoparticle carriers for HIV Env trimer immunogens.

Aleksandar Antanasijevic, George Ueda, Philip J M Brouwer, Jeffrey Copps, Deli Huang, Joel D Allen, Christopher A Cottrell, Anila Yasmeen, Leigh M Sewall, Ilja Bontjer and 12 more

Abstract readEvaluation Study
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
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

47 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Sulfoglycodendron Antivirals with Scalable Architectures and Activities.Journal of chemical information and modeling · 2024
    Article
  9. Article
  10. Sulfoglycodendron Antivirals with Scalable Architectures and Activities.bioRxiv : the preprint server for biology · 2024
    Article
  11. Article
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  13. Article
  14. Article
  15. Article
  16. Review
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  19. 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

22 authors.

Aleksandar AntanasijevicDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0001-9452-8954
George UedaInstitute for Protein Design, Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0002-9792-7149
Philip J M BrouwerAcademic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
Jeffrey CoppsDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0003-4793-7258
Deli HuangDepartment of Immunology and Microbiology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0002-6989-639X
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton, United Kingdom.ORCID 0000-0003-2547-968X
Christopher A CottrellDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0002-3364-3083
Anila YasmeenWeill Cornell Medicine, Cornell University, New York, New York, United States of America.
Leigh M SewallDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0002-2020-2991
Ilja BontjerAcademic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
Thomas J KetasWeill Cornell Medicine, Cornell University, New York, New York, United States of America.
Hannah L TurnerDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0002-4745-8057
Zachary T BerndsenDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0003-4531-9907
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
Per Johan KlasseWeill Cornell Medicine, Cornell University, New York, New York, United States of America.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton, United Kingdom.ORCID 0000-0002-1072-2694
David NemazeeDepartment of Immunology and Microbiology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0002-4769-6311
John P MooreWeill Cornell Medicine, Cornell University, New York, New York, United States of America.
Rogier W SandersAcademic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.ORCID 0000-0002-2324-8573
Neil P KingInstitute for Protein Design, Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0002-2978-4692
David BakerInstitute for Protein Design, Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0001-7896-6217
Andrew B WardDepartment of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, California, United States of America.ORCID 0000-0001-7153-3769

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI AHMED, RAFI · 2012 to 2018
$131.5M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Knock-in mice expressing germline-reverted broadly neutralizing HIV antibodiesR01AI073148 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2007 to 2023
$8.2M
Designing and optimizing candidate HIV vaccines and boosting protocolsR01AI128836 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2017 to 2021
$4.8M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
Broadening autologous Tier 2 anti-HIV neutralizing antibodiesF31AI131873 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI COTTRELL, CHRISTOPHER ANDREW · 2017 to 2020
$95k
Howard Hughes Medical InstituteNIAID NIH HHS F31 AI131873NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI036082NIAID NIH HHS R01 AI073148NIAID NIH HHS R01 AI128836NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Two-component, self-assembling nanoparticles represent a versatile platform for multivalent presentation of viral antigens. Computational design of protein nanoparticles with differing sizes and geometries enables combination with antigens of choice to test novel multimerization concepts in immunization strategies where the goal is to improve the induction and maturation of neutralizing antibody lineages. Here, we describe detailed antigenic, structural, and functional characterization of computationally designed tetrahedral, octahedral, and icosahedral nanoparticle immunogens displaying trimeric HIV envelope glycoprotein (Env) ectodomains. Env trimers, based on subtype A (BG505) or consensus group M (ConM) sequences and engineered with SOSIP stabilizing mutations, were fused to an underlying trimeric building block of each nanoparticle. Initial screening yielded one icosahedral and two tetrahedral nanoparticle candidates, capable of presenting twenty or four copies of the Env trimer. A number of analyses, including detailed structural characterization by cryo-EM, demonstrated that the nanoparticle immunogens possessed the intended structural and antigenic properties. When the immunogenicity of ConM-SOSIP trimers presented on a two-component tetrahedral nanoparticle or as soluble proteins were compared in rabbits, the two immunogens elicited similar serum antibody binding titers against the trimer component. Neutralizing antibody titers were slightly elevated in the animals given the nanoparticle immunogen and were initially more focused to the trimer apex. Altogether, our findings indicate that tetrahedral nanoparticles can be successfully applied for presentation of HIV Env trimer immunogens; however, the optimal implementation to different immunization strategies remains to be determined.

Indexed as

Animalsenv Gene Products, Human Immunodeficiency VirusEpitopesFemaleHIV-1HIV AntibodiesHIV AntigensHIV InfectionsHumansImmunizationNanoparticlesRabbitsenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Antigens

Identifiers

PMID32780770
PMCPMC7418955

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.