ArticleScience translational medicine2025
Computationally designed mRNA-launched protein nanoparticle immunogens elicit protective antibody and T cell responses in mice.
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed.
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- A designed overlapping variant immunogen pool elicits broad sarbecovirus neutralization.bioRxiv : the preprint server for biology · 2026Article
- Current status on encephalitic alphavirus vaccines development: Advances, challenges, and global health perspectives.Infectious medicine · 2026Review
- mRNA delivery of mosaic-8 pan-sarbecovirus RBD vaccines elicits distinct antibody epitope signatures.Cell reports · 2026Article
- Application and Research Progress of Self-Assembling Protein Nanoparticles in Vaccine Development.International journal of molecular sciences · 2026Review
- Review
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- Article
- Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice.Science translational medicine · 2026Article
- A stabilized tandem antigen chimera that elicits potent malaria transmission-reducing activity.Nature communications · 2026Article
- Amplified genome editing bybioRxiv : the preprint server for biology · 2026Article
- De novo design of protein nanoparticles with integrated functional motifs.bioRxiv : the preprint server for biology · 2026Article
- Improving the immunogenicity ofFrontiers in immunology · 2026Article
- Unconventional linkers facilitate potent stabilized coronavirus stem antibody responses following nanoparticle vaccination.bioRxiv : the preprint server for biology · 2025Article
- Broad-spectrum vaccines against various and evolving viruses: from antigen design to nanoparticle delivery.Journal of virology · 2025Review
- SARS-CoV-2 RBD Scaffolded by AP205 or TIP60 Nanoparticles and Delivered as mRNA Elicits Robust Neutralizing Antibody Responses.Vaccines · 2025Article
- Phylogeny-driven design of broadly protective sarbecovirus receptor-binding domain nanoparticle vaccines.bioRxiv : the preprint server for biology · 2025Article
- Breaking barriers: Smart vaccine platforms for cancer immunomodulation.Cancer communications (London, England) · 2025Review
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35 authors.
Funding
Abstract
Messenger RNA (mRNA) vaccines and computationally designed protein nanoparticle vaccines were both clinically derisked and licensed for the first time during the coronavirus disease 2019 (COVID-19) pandemic. These vaccine modalities have complementary immunological benefits that provide strong motivation for their combination. Here, we demonstrate proof of concept for genetic delivery of computationally designed protein nanoparticle immunogens. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model system, we genetically fused a stabilized variant of the Wuhan-Hu-1 spike protein receptor binding domain (RBD) to a protein nanoparticle we previously designed for optimal secretion from human cells. Upon secretion, the nanoparticle formed monodisperse and antigenically intact assemblies displaying 60 copies of the RBD in an immunogenic array. Compared with mRNA vaccines encoding membrane-anchored spike protein and a secreted RBD trimer, an mRNA vaccine encoding the RBD nanoparticle elicited 5- to 28-fold higher titers of neutralizing antibodies in mice. In addition, the "mRNA-launched" RBD nanoparticle vaccine induced higher frequencies of antigen-specific CD8 T cells than the same immunogen delivered as adjuvanted protein and protected mice from either Wuhan-Hu-1 or Omicron BA.5 challenge. These results establish that delivering computationally designed protein nanoparticle immunogens through mRNA can combine the benefits of both vaccine modalities. More broadly, our data highlight the utility of computational protein design in genetic vaccination strategies.
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Registered trials
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.