Evidence map›Paper›PMID 33564763›Full record

ArticlebioRxiv : the preprint server for biology2021

Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 in nonhuman primates following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination.

Matthew J Gorman, Nita Patel, Mimi Guebre-Xabier, Alex Zhu, Caroline Atyeo, Krista M Pullen, Carolin Loos, Yenny Goez-Gazi, Ricardo Carrion, Jing-Hui Tian and 21 more

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

Article in bioRxiv : the preprint server for biology, 2021. 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, 34 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 8 institutions in 1 country.

Matthew J GormanRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Nita PatelNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Mimi Guebre-XabierNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Alex ZhuRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Caroline AtyeoRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Krista M PullenDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Carolin LoosRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Yenny Goez-GaziTexas Biomedical Research Institute. 8715 West Military Drive, San Antonio, TX 78227, USA.
Ricardo CarrionTexas Biomedical Research Institute. 8715 West Military Drive, San Antonio, TX 78227, USA.
Jing-Hui TianNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Dansu YaunRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Kathryn BowmanRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Bin ZhouNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Sonia MaciejewskiNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Marisa E McGrathUniversity of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
James LogueUniversity of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
Matthew B FriemanUniversity of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
David MontefioriDepartment of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Colin MannLa Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Sharon SchendelLa Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Fatima AmanatDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Erica Ollmann SaphireLa Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Douglas LauffenburgerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ann M GreeneNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Alyse D PortnoffNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Michael J MassareNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Larry EllingsworthNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Gregory GlennNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Gale SmithNovavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
Galit AlterRagon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Novavax (United States) · USRagon Institute of MGH, MIT and Harvard · USLa Jolla Institute for Immunology · USUniversity of Maryland, Baltimore · USIcahn School of Medicine at Mount Sinai · USMassachusetts Institute of Technology · USTexas Biomedical Research Institute · USDuke Medical Center · US

Funding

The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7M
COVID Supplement - COMPONENT A OF THE COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTERS (CIVICS) PROGRAM TO DESIGN AND EVALUATE INNOVATIVE INFLUENZA VACCINE APPROACHES,75N93019C00052 · NIAID · UNIVERSITY OF GEORGIA · PI ROSS, TED · 2019 to 2025
$74.6M
Technology CoreU19AI135995 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Kristian Graugaard Andersen · 2018 to 2026
$32.0M
Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
Demystifying the antiviral activity of the IgG3+ antibody responseR37AI080289 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ALTER, GALIT · 2015 to 2022
$5.8M
Immunologic Signatures of SARS-CoV-2 Vaccination and DiseaseU01CA260476 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H. · 2020 to 2024
$3.7M
SARS-CoV-2 Variant TestingR01AI146785 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2020 to 2024
$3.3M
CHLAMYDIA PNEUMONIAE AND MACROPHAGES IN ATHEROSCLEROSISR01AI042790 · NIAID · UNIVERSITY OF WISCONSIN MADISON · PI BYRNE, GERALD IRWIN · 1999 to 2003
$983k
NCI NIH HHS U01 CA260476NIAID NIH HHS 75N93019C00052NIAID NIH HHS R01 AI042790NIAID NIH HHS R01 AI146785NIAID NIH HHS R37 AI080289NIAID NIH HHS T32 AI007387NIAID NIH HHS U19 AI135995NIH HHS P51 OD011133
6 · The paper itself

Abstract

Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants. HIGHLIGHTS: NVX-CoV2373 subunit vaccine elicits receptor blocking, virus neutralizing antibodies, and Fc-effector functional antibodies.The vaccine protects against respiratory tract infection and virus shedding in non-human primates (NHPs).Both neutralizing and Fc-effector functions contribute to protection, potentially through different mechanisms in the upper and lower respiratory tract.Both macaque and human vaccine-induced antibodies exhibit altered Fc-receptor binding to emerging mutants.

Identifiers

PMID33564763
PMCPMC7872351
OpenAlexW3128595283

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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.