Evidence map›Paper›PMID 39924738›Full record

ArticleAdvanced healthcare materials2025

Co-Delivery of Multiple Toll-Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy.

Aaron Ramirez, Jenny E Hernandez-Davies, Aarti Jain, Lu Wang, Erwin Strahsburger, D Huw Davies, Szu-Wen Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced healthcare materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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

7 authors.

Aaron RamirezDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Jenny E Hernandez-DaviesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
Aarti JainVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
Lu WangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.
Erwin StrahsburgerVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
D Huw DaviesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
Szu-Wen WangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA.ORCID 0000-0001-7398-0220

Funding

Tumor-Associated Antigen Delivery using Protein Nanoparticles for Combined ImmunotherapyR01EB027797 · NIBIB · UNIVERSITY OF CALIFORNIA-IRVINE · PI WANG, SZU-WEN · 2019 to 2022
$1.3M
Improving the Immune Response to Nanoparticle-Based SARS-CoV-2 VaccinesR21AI175980 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI WANG, SZU-WEN · 2023 to 2024
$432k
Defense Threat Reduction Agency HDTRA11810036National Science Foundation DMR-2011967National Science Foundation GRFPNIAID NIH HHS R21 AI175980NIBIB NIH HHS R01 EB027797NIH HHS R01EB027797NIH HHS R21AI175980
6 · The paper itself

Abstract

Most seasonal and pandemic influenza vaccines are derived from inactivated or attenuated virus propagated in chicken eggs, while more advanced delivery technologies, such as the use of recombinant proteins and adjuvants, are under-utilized. In this study, the E2 protein nanoparticle (NP) platform is engineered to synthesize vaccines that simultaneously co-deliver influenza hemagglutinin (H5) antigen, TLR5 agonist flagellin (FliCc), and TLR9 agonist CpG 1826 (CpG) all on one particle (termed H5-FliCc-CpG-E2), with uniform molecular orientation significant for immunomodulation. Antigen-bound NP formulations elicit higher IgG antibody responses and broader homosubtypic cross-reactivity against different H5 variants than unconjugated antigen alone. IgG1/IgG2c skewing is modulated by adjuvant type and NP attachment. Conjugation of flagellin to the NP causes significant IgG1 (Th2) skewing while attachment of CpG yields significant IgG2c (Th1) skewing, and simultaneous conjugation of both flagellin and CpG results in a balanced IgG1/IgG2c (Th2/Th1) response. Animals immunized with E2-based NP vaccines and subsequently challenged with H5N1 influenza show 100% survival, and only animals that receive adjuvanted NP formulations are also protected against morbidity. This investigation highlights that NP-based delivery of antigen and multiple adjuvants can be designed to effectively modulate the strength, breadth toward variants, and bias of an immune response against influenza viruses.

Indexed as

Hemagglutinin Glycoproteins, Influenza VirusImmunogenicity, VaccineInfluenza VaccinesNanoparticlesToll-Like ReceptorsAdjuvants, ImmunologicAnimalsAntibodies, ViralFemaleFlagellinImmunoglobulin GInfluenza A Virus, H5N1 SubtypeMiceMice, Inbred BALB COligodeoxyribonucleotidesToll-Like Receptor AgonistsAdjuvants, ImmunologicAntibodies, ViralCpG ODN 1826Flagellinhemagglutinin, avian influenza A virusHemagglutinin Glycoproteins, Influenza VirusImmunoglobulin GInfluenza VaccinesOligodeoxyribonucleotidesToll-Like Receptor AgonistsToll-Like ReceptorsCpGflagellinimmunomodulationinfluenza vaccineprotein nanoparticle

Identifiers

PMID39924738
PMCPMC12004444

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.