Evidence map›Paper›PMID 40882161›Full record

ArticlemBio2025

First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge.

Vincent Dussupt, Jaime L Jensen, Paul V Thomas, Letzibeth Mendez-Rivera, Kerri G Lal, Michelle Zemil McCrea, Isabella Swafford, Joana Hernandez, Rajeshwer S Sankhala, Mekhala Rao and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mBio, 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

30 authors.

Vincent Dussupt *Viral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-8579-6356
Jaime L Jensen *Viral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-8818-7513
Paul V ThomasViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Letzibeth Mendez-RiveraU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Kerri G LalViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Michelle Zemil McCreaU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Isabella SwaffordU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Joana HernandezU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Rajeshwer S SankhalaViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Mekhala RaoU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Juhi AroraU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Agnes HajduczkiViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Ningbo JianU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Phyllis A ReesViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Indica Showell-De LeonU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Gabriel SmithU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Lauren SmithU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Diana WassonU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Annika SchmidU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
I-Ting TengVaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA.
Tongqing ZhouVaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA.ORCID 0000-0002-3935-4637
Peter D KwongVaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA.ORCID 0000-0003-3700-6417
Jeffrey R CurrierViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
William W ReileyTrudeau Institute, Saranac Lake, New York, USA.
Dominic Paquin-ProulxU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Victoria R PolonisU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-4827-9923
Natalie D CollinsViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Nelson L MichaelCenter for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
M Gordon JoyceViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0002-6808-7232
Shelly J KrebsViral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0003-1136-1760

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Sean McSweeney · 2019 to 2026
$38.6M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-naïve and -experienced IndividualsR01AI155983 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Vincent Dussupt · 2021 to 2026
$4.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
National Institute of Allergy and Infectious Diseases R01AI155983NIAID NIH HHS R01 AI155983NIGMS NIH HHS P30 GM124165NIGMS NIH HHS P30 GM133893NIH HHS S10 OD021527U.S. Department of Defense CARES Act
6 · The paper itself

Abstract

Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.2, BA.5, and BQ.1.1. Neutralization potency to these Omicron variants is associated with slower off-rates to the spike protein. Structural characterization of the most potent NTD antibody, WRAIR-2008, revealed a conserved mode of interaction shared with other antibodies of the same multi-donor class. WRAIR-2008 protected mice from weight loss following BA.5 challenge and reduced infectious viral titers in the lungs. Our study highlights the retention of neutralization activity and protection of first-generation VH1-24-derived NTD-directed antibodies to specific Omicron variants and provides valuable insights into the shifting landscape of SARS-CoV-2 variants that are vulnerable to select monoclonal antibodies. IMPORTANCE: As SARS-CoV-2 circulating variants evolve, it is important to understand the vulnerabilities of these viruses to neutralizing antibodies. Within this manuscript, we describe first-generation antibodies isolated following infection with WA-1 that retain viral neutralization to subsequent Omicron variants by targeting a site of viral vulnerability called the NTD. This work highlights the shifting landscape of SARS-CoV-2 variants and provides mechanistic insights into how antibodies from prior infections may play a role in preventing subsequent SARS-CoV-2 variant infections.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCOVID-19SARS-CoV-2AnimalsEpitopesFemaleHumansMiceMice, Inbred BALB CSpike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2monoclonal antibodiesNTDSARS-CoV-2

Identifiers

PMID40882161
PMCPMC12505963

What Socratic holds

Textmetadata
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.