Evidence map›Paper›PMID 40739754›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA.

Parisa Yousefpour, Amrit Raj Ghosh, Himanshi Chawla, Rachel Yeung, Justin Gregory, Kristen Si, Tanaka K Remba, Kristen A Rodrigues, Mariane B Melo, Jonathan Dye and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

17 authors.

Parisa YousefpourKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
Amrit Raj GhoshRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Himanshi ChawlaSchool of Biological Sciences, University of Southampton, SO17 1BJ Southampton, UK.
Rachel YeungKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Justin GregoryKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kristen SiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Tanaka K RembaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kristen A RodriguesKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mariane B MeloKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jonathan DyeKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jon M SteichenConsortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yuebao ZhangDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Yizhou DongIcahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, SO17 1BJ Southampton, UK.
William R SchiefConsortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Moderna, Cambridge, MA 02139, USA.
Facundo D BatistaRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Darrell J IrvineKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: djirvine@scripps.edu.

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
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Investigating the Protective Efficacy of SIV/HIV T and B cell Immunity Induced by RNA RepliconsR01AI176533 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Gaurav Das Gaiha · 2023 to 2026
$3.5M
Controlling Vaccine Kinetics with Small Molecule DrugsF32AI164829 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YOUSEFPOUR, PARISA · 2022 to 2024
$184k
Gates Foundation INV-008813Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NIAID NIH HHS F32 AI164829NIAID NIH HHS R01 AI176533NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

mRNA vaccines have emerged as an important platform for vaccine development. Unlike protein subunit vaccines, mRNA-expressed antigens can be expressed in either secreted or transmembrane (TM) forms mimicking a viral envelope (Env) protein. Here, we investigated the impact of antigen expression format on the antigenicity profile, glycosylation, and immunogenicity of stabilized HIV Env trimer immunogens expressed from self-replicating RNA (replicon) vaccines. Replicon-encoded trimers in both forms exhibited proper folding, and replicon-expressed secreted trimers exhibited glycosylation patterns largely consistent with recombinant trimer protein, although with enrichment of complex glycans over high mannose at some sites. Both formats were highly immunogenic in mice, eliciting comparable serum antibody and T cell responses. Interestingly, the TM format initiated smaller germinal center (GC) responses, but these GCs were enriched for trimer-binding B cells compared to secreted trimer vaccines. In a B cell receptor knockin adoptive transfer model for assessing germline targeting, the replicon-encoded TM trimer elicited a greater frequency of epitope-targeting antibodies and recruited broadly neutralizing antibody precursor B cells to the GC response more efficiently compared to the replicon-encoded secreted trimer or protein trimer combined with adjuvant. These results indicate that the form of immunogen expression can impact key elements of immune responses to RNA vaccines.

Indexed as

AIDS Vaccinesenv Gene Products, Human Immunodeficiency VirusHIV-1HIV InfectionsImmunity, HumoralAnimalsAntibodies, NeutralizingB-LymphocytesEpitopesFemaleGerminal CenterGlycosylationHIV AntibodiesHumansMicemRNA VaccinesAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesmRNA VaccinesBG18expression formHIV bnAbsHIV trimerreplicon RNARNA vaccines

Identifiers

PMID40739754
PMCPMC12425358

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.