Evidence map›Paper›PMID 40482923›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

Optimizing delivery in a multivalent subunit influenza vaccine using mixed polymeric microparticle degradation rates.

Erik S Pena, Luis Ontiveros-Padilla, Nicole R Lukesh, Grace L Williamson, Connor T Murphy, Dylan A Hendy, John A Roque, Michael A Carlock, Ted M Ross, Kristy M Ainslie and 1 more

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Erik S PenaDepartment of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, NC, USA.
Luis Ontiveros-PadillaDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Nicole R LukeshDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Grace L WilliamsonDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Connor T MurphyDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Dylan A HendyDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
John A RoqueDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Michael A CarlockFlorida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA.
Ted M RossFlorida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA; Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA; Department of Infectious Diseases, University of Georgia, Athens, GA, USA.; Department of Infection Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.
Kristy M AinslieDepartment of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, NC, USA; Division of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA; Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: ainsliek@email.unc.edu.
Eric M BachelderDivision of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.

Funding

Micro-Particle Delivery of a Potent Intracellular Adjuvant for a Universal Flu VaccineR01AI141333 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BACHELDER, ERIC, TING, JENNY P · 2019 to 2023
$5.9M
Optimizing a Universal Influenza Subunit Nano/Microparticulate VaccineR01AI147497 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AINSLIE, KRISTY M · 2020 to 2024
$2.9M
NIAID NIH HHS R01 AI141333NIAID NIH HHS R01 AI147497
6 · The paper itself

Abstract

The influenza virus continues to impose a significant yearly burden on society due to the variable efficacy of seasonal vaccines. Further strains like H5N1, that are not included in the seasonal influenza vaccine, may spill over from animal reservoirs and more significantly impact human health. A broadly acting subunit vaccine can offer protection across multiple strains but would have low immunogenicity without an adjuvant, which are currently limited and require delivery systems to mitigate side effects. Further, antigen delivery can be enhanced with carrier systems to provide dose sparing, and thermostability. This study explores acetalated dextran microparticles (Ace-DEX MPs) encapsulating cGAMP and computational optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins, to form a multivalent influenza vaccine. Previous research has shown that Ace-DEX cGAMP MPs with varying degradation kinetics can modulate the immune response. Here, we investigate the effects of mixing MPs with different degradation rates to optimize the immune response. Mice vaccinated with slower-degrading cGAMP MPs exhibited higher IgG2a titers and IL-2 producing splenocytes, while those vaccinated with a mix of fast and slow-degrading cGAMP MPs had the highest IFN-γ producing splenocytes. The protection afforded in mice was also shown in ferrets with a H1, H3 and H5 trivalent COBRA formulation adjuvanted by slow degrading cGAMP MPs. Furthermore, using Ace-DEX MPs encapsulating two broadly reactive COBRA H1 and H3 immunogens in particles with fast and slow degradation rates, co-delivered with cGAMP MPs, resulted in less single antigen dominance when the more dominant antigen was encapsulated in the slowest degrading MP. This work underscores the utility of Ace-DEX MPs as a vaccine delivery platform and the impact of MP degradation kinetics on vaccine efficacy.

Indexed as

DextransHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesAnimalsFemaleImmunoglobulin GInterleukin-2MiceMice, Inbred BALB CNucleotides, CyclicOrthomyxoviridae InfectionsVaccines, Subunitcyclic guanosine monophosphate-adenosine monophosphateDextransHemagglutinin Glycoproteins, Influenza VirusImmunoglobulin GInfluenza VaccinesInterleukin-2Nucleotides, CyclicVaccines, SubunitAcetalated dextranAntibody responseCellular responseFlu vaccineNanoparticlesTunable release

Identifiers

PMID40482923
PMCPMC12255521

What OpenQuestion holds

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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.