Evidence map›Paper›PMID 41292804›Full record

ArticlebioRxiv : the preprint server for biology2025

Functional Activity of HIV-1 bNAbs Across Diverse Strains is Driven by Binding Site and Can be Enhanced Through Fc Engineering.

Chia Jung Li, Eunice Lim, Meredith Phelps, Jacqueline M Brady, Vintus Okonkwo, Caitlin McCarthy, Caroline Alexander, Margaret E Ackerman, Daniel Lingwood, Alejandro B Balazs

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Chia Jung LiRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Eunice LimRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Meredith PhelpsRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Jacqueline M BradyRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Vintus OkonkwoRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Caitlin McCarthyRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Caroline AlexanderRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.
Margaret E AckermanThayer School of Engineering, Dartmouth College; Hanover, NH 03755, USA.ORCID 0000-0002-4253-3476
Daniel LingwoodRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.ORCID 0000-0001-5631-9238
Alejandro B BalazsRagon Institute of Mass General Brigham, MIT, and Harvard, Cambridge; MA, 02139, USA.ORCID 0000-0002-1767-3944

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
Polyclonal Bi-Specific Vectored ImmunoTherapy to Functionally Cure HIV InfectionDP1DA060607 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI Alejandro Benjamin Balazs · 2024 to 2026
$3.2M
Innate-like BCR activity as a template for universal vaccination against influenza virusR01AI137057 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2018 to 2022
$2.6M
Engineering Humoral Immunity to Functionally Cure HIV InfectionDP2DA040254 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI BALAZS, ALEJANDRO BENJAMIN · 2015 to 2015
$2.6M
Eliminating the Immunogenicity of AAV Vectored HIV Antibody DeliveryR01AI174276 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Alejandro Benjamin Balazs · 2024 to 2026
$2.5M
Triggering germline-encoded broadly neutralizing antibody responses against influenza virusR01AI153098 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI BATISTA, FACUNDO DAMIAN, LINGWOOD, DANIEL · 2020 to 2023
$2.1M
Systemic coordination of pro-inflammatory immune reactions through dendritic cell-restricted sIL6R biogenesisR01AI155447 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2021 to 2025
$2.0M
AAV Vectored Delivery of Broadly Neutralizing Antibodies with Optimal Innate Functionality Against HIVR01AI174875 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI BALAZS, ALEJANDRO BENJAMIN · 2023 to 2024
$1.6M
NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI137057NIAID NIH HHS R01 AI153098NIAID NIH HHS R01 AI155447NIAID NIH HHS R01 AI174276NIAID NIH HHS R01 AI174875NIDA NIH HHS DP1 DA060607NIDA NIH HHS DP2 DA040254
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bNAbs) are promising tools for HIV-1 treatment and prevention, due to their ability to mediate both Fab-dependent neutralization and Fc-dependent effector functions. While antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) have been implicated in antiviral activity, the extent to which these functions vary across bNAb epitopes, viral strains, and Fc region remains unclear. Here, we systematically evaluated twenty bNAbs targeting five distinct Env epitopes against a diverse panel of nine HIV-1 strains. We found that epitope specificity and Env sequence both critically influenced bNAb effector functions. CD4 binding site (CD4bs)- and V3 glycan-targeting bNAbs mediated the broadest and most potent ADCC and ADCP, while V1/V2 apex-directed bNAbs preferentially induced ADCP. In contrast, MPER-targeting bNAbs triggered ADCC more selectively, and gp120/gp41 interface-targeting bNAbs showed limited activity. Irrespective of binding epitope, different strains exhibited a broad range of effector function sensitivities. To investigate the impact of Fc modifications on this variability, we subclass-switched and introduced previously identified Fc mutations known to change Fcγ receptor affinity. Some of these mutations significantly boosted ADCC, while IgG3 subclass switching dramatically enhanced ADCP, even against highly resistant strains. Collectively, these results demonstrate that effector function is shaped by both antibody specificity and viral Env context and that rational Fc modification has the potential to improve antibody-based therapeutics against HIV.

Indexed as

ADCCADCPEnv sequenceFc engineeringHIV bNAb

Identifiers

PMID41292804
PMCPMC12642679

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.