Evidence map›Paper›PMID 42059889›Full record

ArticleeLife2026

Bivalent mRNA booster encoding virus-like particles elicits potent polyclass receptor-binding domain antibodies in pre-vaccinated mice.

Chengcheng Fan, Alexander A Cohen, Kim-Marie A Dam, Annie V Rorick, Ange-Célia I Priso Fils, Zhi Yang, Priyanthi N P Gnanapragasam, Luisa N Segovia, Kathryn E Huey-Tubman, Woohyun J Moon and 3 more

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Chengcheng Fan *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.ORCID https://orcid.org/0000-0003-4213-5758
Alexander A Cohen *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.ORCID https://orcid.org/0000-0002-2818-656X
Kim-Marie A Dam *Gladstone Institutes, San Francisco, United States.ORCID https://orcid.org/0000-0002-1416-4757
Annie V RorickDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Ange-Célia I Priso FilsDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Zhi YangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.ORCID https://orcid.org/0000-0001-8680-3784
Priyanthi N P GnanapragasamDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Luisa N SegoviaDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Kathryn E Huey-TubmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
Woohyun J MoonAcuitas Therapeutics, Vancouver, Canada.
Paulo J C LinAcuitas Therapeutics, Vancouver, Canada.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.ORCID https://orcid.org/0000-0002-2277-3990
Magnus A G HoffmannGladstone Institutes, San Francisco, United States.ORCID https://orcid.org/0000-0003-4923-9568

Funding

Self-Assembling Spike-EBR Nanoparticles as a Vaccine Platform Technology Against SARS-CoV-2 and Future Pandemic Coronaviruses.DP5OD033362 · OD · J. DAVID GLADSTONE INSTITUTES · PI HOFFMANN, MAGNUS ADRIAN GERO · 2022 to 2025
$2.3M
Determining the role of antibody epitope specificity in regulating Fc effector functionsK99AI185267 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Alexander A Cohen · 2025 to 2026
$257k
Gates Foundation INV-034638Gates Foundation INV-056219NIAID NIH HHS K99 AI185267NIH HHS DP5 OD033362NIH HHS DP5OD033362NIH HHS P01-AI165075
6 · The paper itself

Abstract

mRNA vaccines emerged as a leading vaccine technology during the COVID-19 pandemic. However, their sustained protective efficacies were limited by relatively short-lived antibody responses and the emergence of SARS-CoV-2 variants, necessitating frequent and variant-updated boosters. We recently developed the ESCRT- and ALIX-binding region (EABR) mRNA vaccine platform, which encodes engineered immunogens that induce budding of enveloped virus-like particles (eVLPs) from the plasma membrane, thereby resulting in presentation of immunogens on cell surfaces and eVLPs. Prior studies showed that spike (S)-EABR mRNA-LNP immunizations elicited enhanced neutralizing antibody responses against ancestral and variant SARS-CoV-2 compared with conventional S mRNA-LNP in naïve mice, but the effectiveness of S-EABR mRNA-LNP boosters in the context of pre-existing immunity has not been investigated. Here, we evaluated monovalent Wuhan-Hu-1 (Wu1) and bivalent (Wu1/BA.5) S-EABR mRNA-LNP boosters in mice pre-vaccinated with conventional Wu1 S mRNA-LNP. Compared to conventional S mRNA-LNP boosters, the EABR approach enhanced monovalent and bivalent mRNA-LNP booster-induced neutralizing responses against Omicron subvariants BA.1, BA.5, BQ.1.1, and XBB.1, with bivalent S-EABR mRNA-LNP consistently eliciting the highest titers. Epitope mapping of polyclonal antisera by deep mutational scanning revealed that bivalent S-EABR mRNA-LNP boosted diverse 'polyclass' anti-receptor-binding domain (RBD) responses, suggesting balanced targeting of multiple RBD epitope classes. In contrast, monovalent S, bivalent S, and monovalent S-EABR mRNA-LNP boosters elicited less diverse polyclonal serum responses primarily targeting immunodominant RBD epitopes. Cryo-electron microscopy (cryo-EM) structures demonstrated that bivalent mRNA immunizations promote S heterotrimer formation, potentially enhancing bivalent S-EABR mRNA-LNP booster-induced antibody breadth and polyclass epitope targeting by activating cross-reactive B cells through intra-S crosslinking. These findings support the future design of bivalent or multivalent S-EABR mRNA-LNP boosters as a promising strategy to confer broader, and therefore potentially more durable, protection against emerging SARS-CoV-2 variants and other rapidly evolving viruses.

Indexed as

Antibodies, ViralCOVID-19COVID-19 VaccinesSARS-CoV-2Vaccines, Virus-Like ParticleAnimalsAntibodies, NeutralizingFemaleImmunization, SecondaryMiceRNA, MessengerSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesRNA, MessengerSpike Glycoprotein, CoronavirusVaccines, Virus-Like Particleepitope targetingimmune imprintinginfectious diseasemicrobiologymousemRNA vaccinesSARS-CoV-2

Identifiers

PMID42059889
PMCPMC13132547

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.