Evidence map›Paper›PMID 36032975›Full record

ArticlebioRxiv : the preprint server for biology2023

Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds.

Eike-Christian Wamhoff, Larance Ronsard, Jared Feldman, Grant A Knappe, Blake M Hauser, Anna Romanov, Evan Lam, Kerri St Denis, Julie Boucau, Amy K Barczak and 4 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, 20 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Eike-Christian WamhoffDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Larance RonsardRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Jared FeldmanRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Grant A KnappeDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Blake M HauserRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Anna RomanovDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Evan LamRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Kerri St DenisRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Julie BoucauRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Amy K BarczakRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Alejandro B BalazsRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Aaron SchmidtRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Daniel LingwoodRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, United States.
Mark BatheDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Ragon Institute of MGH, MIT and Harvard · USMassachusetts Institute of Technology · USBroad Institute · USHarvard University · US

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
Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Epitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2M
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
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
CDRH3-independent B cell stimulation to selectively expand VRC01 lineages from a fully humanized immunoglobulin repertoireR01AI124378 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI CHACKERIAN, BRYCE C, LINGWOOD, DANIEL · 2017 to 2020
$2.0M
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
Structured DNA Nanoparticles Therapeutic mRNA and CRISPR/Cas9 DeliveryR21EB026008 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BATHE, MARK · 2018 to 2021
$796k
NIAID NIH HHS F30 AI160908NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI124378NIAID NIH HHS R01 AI146779NIAID NIH HHS R01 AI153098NIAID NIH HHS R01 AI155447NIAID NIH HHS T32 AI007245NIAID NIH HHS U19 AI057229NIBIB NIH HHS R21 EB026008NIDA NIH HHS DP2 DA040254NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo- and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.

Identifiers

PMID36032975
PMCPMC9413718
OpenAlexW4293011251

What OpenQuestion 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 OpenQuestion graph.