Evidence map›Paper›PMID 40373766›Full record

ArticleStructure (London, England : 1993)2025

A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.

Mohammad M Sajadi, Abdolrahim Abbasi, Zahra Rikhtegaran Tehrani, Christine Siska, Rutilio Clark, Woo Chi, Michael S Seaman, Dieter Mielke, Kshitij Wagh, Qingbo Liu and 36 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors.

Mohammad M SajadiDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, Maryland VA Healthcare System, Baltimore, MD, USA. Electronic address: msajadi@ihv.umaryland.edu.
Abdolrahim AbbasiDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Zahra Rikhtegaran TehraniDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Christine SiskaJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Rutilio ClarkJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Woo ChiJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Dieter MielkeDuke Human Vaccine Institute, Durham, NC, USA.
Kshitij WaghDuke Human Vaccine Institute, Durham, NC, USA.
Qingbo LiuKey Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China.
Taylor JumpaJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Randal R KetchemJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Dung N NguyenInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
William D TolbertInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Brian G PierceUniversity of Maryland Institute for Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
Ben AtkinsonDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Derrick DemingJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Megan SpragueJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Andrew AsakawaJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
David FerrerJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Yasmin DunnJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Sarah CalvilloJust-Evotec Biologics, 401 Terry Avenue North, Seattle, WA, USA.
Rui YinUniversity of Maryland Institute for Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
Johnathan D GuestUniversity of Maryland Institute for Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
Bette KorberTheoretical Biology & Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Bryan T MayerVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Alicia H SatoVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Xin OuyangDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Scott FoulkeDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Parham HabibzadehDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Maryam KarimiDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Arash AslanabadiDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Mahsa HojabriDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Saman SaadatDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Roza ZareidoodejiDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Mateusz KędziorNeutralizing Antibody Center, IAVI, La Jolla, CA, USA.
Edwin PozharskiUniversity of Maryland Institute for Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
Alonso HerediaDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Hegang ChenDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
David MontefioriDivision of Surgical Sciences, Duke University School of Medicine, Durham, NC, USA.
Guido FerrariDuke Human Vaccine Institute, Durham, NC, USA; Division of Surgical Sciences, Duke University School of Medicine, Durham, NC, USA.
Marzena PazgierInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
George K LewisDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Joseph G JardineDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Paolo LussoLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Anthony DeVicoDivisions of Vaccine Research and Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.

Funding

Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Structure-Function Analytics CoreP01AI162242 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2021 to 2025
$22.2M
Novel bNAB-based treatment and prevention of HIV-1R01AI155150 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI SAJADI, MOHAMMAD MOHSENI · 2021 to 2024
$2.8M
A new strategy to eliminate HIV-1-infected cells by unlocking the Env trimerR01AI174908 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Marzena Elzbieta Pazgier · 2023 to 2026
$2.8M
Engineering of pan-neutralizing anti-HIV envelope antibodiesR01AI147870 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI SAJADI, MOHAMMAD MOHSENI · 2020 to 2024
$2.5M
High resolution modeling and design of immune recognitionR35GM144083 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI Brian G. Pierce · 2022 to 2026
$1.6M
BLRD VA I01 BX004525Gates Foundation INV-005284Gates Foundation INV-036842NIAID NIH HHS P01 AI131251NIAID NIH HHS P01 AI162242NIAID NIH HHS R01 AI147870NIAID NIH HHS R01 AI155150NIAID NIH HHS R01 AI174908NIGMS NIH HHS R35 GM144083
6 · The paper itself

Abstract

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first-generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing Current Good Manufacturing Practices (cGMP) manufacturing capability. Here, we report the engineering of an anti-CD4-binding site (CD4bs) bnAb, N49P9.3. Through a series of rational modifications, we produced a variant, N49P9.6-FR-LS, that demonstrates enhanced potency, superior antiviral activity in combination with other bnAbs, low polyreactivity, and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

Indexed as

Antibodies, NeutralizingHIV-1HIV AntibodiesProtein EngineeringAnimalsBroadly Neutralizing AntibodiesCD4 AntigensHIV InfectionsHumansAntibodies, NeutralizingBroadly Neutralizing AntibodiesCD4 AntigensHIV AntibodiesADCCbnAbCD4 binding sitecombination therapieselite neutralizerengineeringHIVHIV curemonoclonal antibodyneutralization

Identifiers

PMID40373766
PMCPMC12227296

What OpenQuestion holds

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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 OpenQuestion graph.