Evidence map›Paper›PMID 38187726›Full record

ArticlebioRxiv : the preprint server for biology2023

Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

R Dilshan Malewana, Victoria Stalls, Aaron May, Xiaozhi Lu, David R Martinez, Alexandra Schäfer, Dapeng Li, Maggie Barr, Laura L Sutherland, Esther Lee and 35 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 6 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors at 8 institutions in 5 countries.

R Dilshan MalewanaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0003-4207-4318
Victoria StallsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Aaron MayDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Xiaozhi LuDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
David R MartinezDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Dapeng LiDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Maggie BarrDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Laura L SutherlandDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Esther LeeDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Robert ParksDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Whitney Edwards BeckDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Amanda NewmanDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Kevin W BockInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
Mahnaz MinaiInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
Bianca M NagataInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
C Todd DeMarcoDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Thomas N DennyDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Thomas H OguinDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Wes RountreeDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Yunfei WangDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Katayoun MansouriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Robert J EdwardsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Gregory D SempowskiDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Amanda EatonDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Hiromi MuramatsuDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rory HendersonDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Ying TamAcuitas Therapeutics, LLC, Vancouver, BC, V6T 1Z3, Canada.
Christopher BarbosaAcuitas Therapeutics, LLC, Vancouver, BC, V6T 1Z3, Canada.
Juanjie TangDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD 20871, USA.
Derek W CainDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Sampa SantraBeth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Ian N MooreInfectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
Hanne AndersenBIOQUAL, Rockville, Rockville, MD 20850, USA.
Mark G LewisBIOQUAL, Rockville, Rockville, MD 20850, USA.
Hana GoldingDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD 20871, USA.
Robert SederVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
Surender KhuranaDivision of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD 20871, USA.
David C MontefioriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Norbert PardiDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Drew WeissmanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Priyamvada AcharyaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Kevin O SaundersDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-7399-7954
International Vaccine Institute · KRNational Institutes of Health · USCenter for Biologics Evaluation and Research · USUniversity of North Carolina at Chapel Hill · USUniversity of Pennsylvania · USAcuitas Therapeutics (Canada) · CABioqual · USBeth Israel Deaconess Medical Center · US

Funding

Project 4: Computational panbetaCoV immunogen designP01AI158571 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2021 to 2023
$28.0M
Project 2 - GMP Manufacturing of mRNA ImmunogensU19AI142596 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2024
$19.0M
Regional Biocontainment Laboratory (RBL)UC6AI058607 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, R SANDERS · 2003 to 2005
$16.3M
Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC)U01AI151378 · NIAID · RESEARCH TRIANGLE INSTITUTE · PI Gregory D Sempowski · 2020 to 2026
$14.7M
HIV-1 gp140 Oligomers as Vaccine ImmunogensP01AI048280 · NIAID · The Johns Hopkins University · PI QUINNAN, GERALD V. · 2001 to 2003
$4.6M
Project 3: Targeting Neurokinin 1 ReceptorP01MH105303 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI DOUGLAS, STEVEN DANIEL, FISCHER, TRACY · 2014 to 2017
$4.3M
Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responsesR01AI153064 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michela Locci, Norbert Pardi · 2020 to 2026
$4.2M
Development of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNAR01AI146101 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PARDI, NORBERT · 2019 to 2023
$3.1M
NIAID NIH HHS P01 AI048280NIAID NIH HHS P01 AI158571NIAID NIH HHS R01 AI146101NIAID NIH HHS R01 AI153064NIAID NIH HHS U01 AI151378NIAID NIH HHS U19 AI142596NIAID NIH HHS UC6 AI058607NIMH NIH HHS P01 MH105303
6 · The paper itself

Abstract

Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOCs including Omicron XBB.1.5, but lacked cross-Sarbecovirus neutralization. Structural analysis showed that the macaque broad SARS-CoV-2 VOC nAbs bound to the same epitope as a human broad SARS-CoV-2 VOC nAb, DH1193. Vaccine-induced antibodies that targeted the RBD inner face neutralized multiple Sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike lacking proline substitutions encoded by nucleoside-modified mRNA can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human Sarbecoviruses or recent Omicron VOCs.

Identifiers

PMID38187726
PMCPMC10769253
OpenAlexW4390012746

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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.