Evidence map›Paper›PMID 37940661›Full record

ArticleNature communications2023

Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility.

Kemin Tan, Junjian Chen, Yu Kaku, Yi Wang, Luke Donius, Rafiq Ahmad Khan, Xiaolong Li, Hannah Richter, Michael S Seaman, Thomas Walz and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

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

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 3 countries.

Kemin Tan *Structural Biology Center, X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Lemont, IL, USA.ORCID 0000-0002-4003-7903
Junjian Chen *Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Yu KakuLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Yi WangLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Luke DoniusLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Rafiq Ahmad KhanLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-4321-5557
Xiaolong LiLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6549-4089
Hannah RichterCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Thomas WalzLaboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY, USA.
Wonmuk HwangDepartment of Biomedical Engineering, Texas A&M University, College Station, TX, USA.
Ellis L ReinherzLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. ellis_reinherz@dfci.harvard.edu.ORCID 0000-0003-1048-5526
Mikyung KimLaboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. mikyung_kim@dfci.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USArgonne National Laboratory · USRockefeller University · USTexas A&M University · USUniversity of Science and Technology of China · CN

Funding

Targeting Immunogenicity to the MPER Hinge and C-helix for BNAb ElicitationP01AI126901 · NIAID · DANA-FARBER CANCER INST · PI REINHERZ, ELLIS L · 2016 to 2020
$9.2M
Approaches to inducing broadly neutralizing antibodies with immunogens mimicking steric occlusion of the MPER as configured on the HIV-1virion surfaceR01AI145509 · NIAID · DANA-FARBER CANCER INST · PI KIM, MIKYUNG · 2019 to 2022
$1.8M
NIAID NIH HHS P01 AI126901NIAID NIH HHS R01 AI145509
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bnAbs) against HIV-1 target conserved envelope (Env) epitopes to block viral replication. Here, using structural analyses, we provide evidence to explain why a vaccine targeting the membrane-proximal external region (MPER) of HIV-1 elicits antibodies with human bnAb-like paratopes paradoxically unable to bind HIV-1. Unlike in natural infection, vaccination with MPER/liposomes lacks a necessary structure-based constraint to select for antibodies with an adequate approach angle. Consequently, the resulting Abs cannot physically access the MPER crawlspace on the virion surface. By studying naturally arising Abs, we further reveal that flexibility of the human IgG3 hinge mitigates the epitope inaccessibility and additionally facilitates Env spike protein crosslinking. Our results suggest that generation of IgG3 subtype class-switched B cells is a strategy for anti-MPER bnAb induction. Moreover, the findings illustrate the need to incorporate topological features of the target epitope in immunogen design.

Indexed as

HIV-1HIV InfectionsVaccinesAntibodies, NeutralizingBinding Sites, AntibodyBroadly Neutralizing AntibodiesEpitopesHIV AntibodiesHIV Envelope Protein gp41HumansImmunoglobulin GAntibodies, NeutralizingBroadly Neutralizing AntibodiesEpitopesHIV AntibodiesHIV Envelope Protein gp41Immunoglobulin GVaccines

Identifiers

PMID37940661
PMCPMC10632514
OpenAlexW4388488113

What OpenQuestion 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 OpenQuestion graph.