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Administration of antigenically distinct influenza viral particle combinations as an influenza vaccine strategy.

作者信息

Zhu Xinyu, Luo Zhaochen, Leonard Rebecca A, Hamele Cait E, Spreng Rachel L, Heaton Nicholas S

机构信息

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.

出版信息

PLoS Pathog. 2025 Jan 22;21(1):e1012878. doi: 10.1371/journal.ppat.1012878. eCollection 2025 Jan.


DOI:10.1371/journal.ppat.1012878
PMID:39841684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11753672/
Abstract

One approach for developing a more universal influenza vaccine is to elicit strong immune responses against canonically immunosubdominant epitopes in the surface exposed viral glycoproteins. While standard vaccines typically induce responses directed primarily against mutable epitopes in the hemagglutinin (HA) head domain, there are generally limited or variable responses directed against epitopes in the relatively more conserved HA stalk domain and neuraminidase (NA) proteins. Here we describe a vaccine approach that utilizes a combination of wildtype (WT) influenza virus particles along with virus particles engineered to display a trimerized HA stalk in place of the full-length HA protein to elicit both responses simultaneously. After initially generating the "headless" HA-containing viral particles in the A/Hawaii/70/2019 (HI/19) genetic background and demonstrating the ability to elicit protective immune responses directed against the HA-stalk and NA, we co-formulated those virions with unmodified WT viral particles. The combination vaccine elicited "hybrid" and protective responses directed against the HA-head, HA-stalk, and NA proteins in both naïve and pre-immune mice and ferrets. Collectively, our results highlight a potentially generalizable method combining viral particles with differential antigenic compositions to elicit broader immune responses that may lead to more durable protection from influenza disease post-vaccination.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/51f1662ce7fb/ppat.1012878.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/86b18e03aadb/ppat.1012878.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/d55002fb8659/ppat.1012878.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/ed9a8dfa9f25/ppat.1012878.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/05277b65ef97/ppat.1012878.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/51f1662ce7fb/ppat.1012878.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/86b18e03aadb/ppat.1012878.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/d55002fb8659/ppat.1012878.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/ed9a8dfa9f25/ppat.1012878.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/05277b65ef97/ppat.1012878.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/11753672/51f1662ce7fb/ppat.1012878.g005.jpg

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[1]
Administration of antigenically distinct influenza viral particle combinations as an influenza vaccine strategy.

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[2]
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[3]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Research Progress of Universal Influenza Vaccine.

Vaccines (Basel). 2025-8-15

本文引用的文献

[1]
Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

J Virol. 2024-10-22

[2]
Immunodominance hierarchy after seasonal influenza vaccination.

Emerg Microbes Infect. 2022-12

[3]
A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection.

Viruses. 2022-6-14

[4]
Reactogenicity, safety, and immunogenicity of chimeric haemagglutinin influenza split-virion vaccines, adjuvanted with AS01 or AS03 or non-adjuvanted: a phase 1-2 randomised controlled trial.

Lancet Infect Dis. 2022-7

[5]
Broadly neutralizing antibodies target a haemagglutinin anchor epitope.

Nature. 2022-2

[6]
Mosaic Hemagglutinin-Based Whole Inactivated Virus Vaccines Induce Broad Protection Against Influenza B Virus Challenge in Mice.

Front Immunol. 2021

[7]
Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients.

Signal Transduct Target Ther. 2021-9-24

[8]
Universal Influenza Virus Neuraminidase Vaccine Elicits Protective Immune Responses against Human Seasonal and Pre-pandemic Strains.

J Virol. 2021-8-10

[9]
Engineered influenza virions reveal the contributions of non-hemagglutinin structural proteins to vaccine mediated protection.

J Virol. 2021-4-26

[10]
Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients.

Cell Rep Med. 2020-11-17

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