Evidence map›Paper›PMID 38753808›Full record

ArticleScience immunology2024

mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models.

Xuesong Wang, Christopher A Cottrell, Xiaozhen Hu, Rashmi Ray, Maria Bottermann, Paula Maldonado Villavicencio, Yu Yan, Zhenfei Xie, John E Warner, Jordan Renae Ellis-Pugh and 17 more

Abstract read
In one paragraph

Article in Science immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed.

  1. Trial
  2. Trial
  3. New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026
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  19. Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025
    Article
  20. Article
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

27 authors.

Xuesong WangRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0003-8996-1501
Christopher A CottrellDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-3364-3083
Xiaozhen HuDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-3890-0533
Rashmi RayRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-4794-3124
Maria BottermannRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-8178-100X
Paula Maldonado VillavicencioRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Yu YanRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-2756-4899
Zhenfei XieRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0006-9341-4721
John E WarnerRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Jordan Renae Ellis-PughRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0009-0000-4155-3566
Oleksandr KalyuzhniyDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-5273-1951
Alessia LiguoriDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8606-574X
Jordan R WillisDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-0135-5263
Sergey MenisDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Sebastian RämischDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-1801-4983
Saman EskandarzadehDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-0671-0770
Michael KubitzDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Ryan TingleDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-2874-7010
Nicole PhelpsDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-9613-3921
Bettina GroschelDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-3127-5448
Sunny HimansuModerna Inc., Cambridge, MA 02139, USA.ORCID 0000-0002-7954-9674
Andrea CarfiModerna Inc., Cambridge, MA 02139, USA.
Kathrin H KirschRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Stephanie R WeldonRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0001-5384-9946
Usha NairRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-1927-6889
William R SchiefRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-1120-0150
Facundo D BatistaRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-1130-9463

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.

Indexed as

Broadly Neutralizing AntibodiesNanoparticlesRNA, MessengerAIDS VaccinesAnimalsAntibodies, MonoclonalAntibodies, NeutralizingFemaleHIV-1HIV AntibodiesHIV InfectionsHumansLipidsLiposomesMiceAIDS VaccinesAntibodies, MonoclonalAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV AntibodiesLipid NanoparticlesLipidsLiposomesRNA, MessengerVRC01 monoclonal antibody

Identifiers

PMID38753808
PMCPMC11488661

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Registered trials

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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.