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基于多价H3 COBRA的流感疫苗在免疫前老年雪貂模型中引发增强的免疫反应。

Multivalent H3 COBRA-based influenza vaccine elicits enhanced immune response in a pre-immune elderly ferret model.

作者信息

Zhang Xiaojian, Shi Hua, Ross Ted M

机构信息

Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.

Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA; Department of Infectious Diseases, University of Georgia, Athens, GA, USA; Florida Research and Innovation Center, Cleveland, Clinic, Port Saint Lucie, FL, USA; Department of Infection Biology, Lehner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Vaccine. 2025 May 22;56:127156. doi: 10.1016/j.vaccine.2025.127156. Epub 2025 Apr 22.


DOI:10.1016/j.vaccine.2025.127156
PMID:40267617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12264823/
Abstract

Influenza viruses cause significant mortality in humans, especially among people 65 years and older. The outbreaks of A(H3N2) influenza viruses or viruses of vaccine-mismatched strains are usually associated with more severe diseases in elderly population. Vaccination is the practical countermeasure for controlling influenza virus infection in humans. However, the immune responses elicited by current influenza vaccines in elderly are not as robust as those responses elicited in younger adults. There is an urgent need for a universal influenza virus vaccine that can induce broadly protective immunity against viral infection in elderly individuals. Currently, influenza virus vaccines that target conserved epitopes on a variety of influenza virus antigens are under evaluation. However, almost all these vaccine candidates are evaluated in adult animal models. In this study, we evaluated Computationally Optimized Broadly Reactive Antigen (COBRA)-based influenza vaccines in elderly ferrets with pre-existing immunity to historical influenza viruses to assess the breadth of vaccine induced protective antibody responses. Vaccination of elderly ferrets with Infectimune® adjuvanted mixtures of COBRA hemagglutinin (HA) and neuraminidase (NA) recombinant protein vaccines elicited robust binding antibodies against all components in the vaccine. Vaccine formulations with multiple H3 COBRA HA components significantly enhanced hemagglutination-inhibition (HAI) activity against H3N2 viruses. In addition, elderly ferrets vaccinated with multivalent COBRA HA and NA vaccines were protected from infection with reduced nasal virus shedding. Overall, a multivalent COBRA HA and NA vaccine may be an effective vaccine strategy to reduce morbidity and mortality in the elderly.

摘要

流感病毒会导致人类大量死亡,尤其是65岁及以上的人群。甲型(H3N2)流感病毒或疫苗匹配不当毒株引发的疫情通常会在老年人群中导致更严重的疾病。接种疫苗是控制人类流感病毒感染的切实可行对策。然而,目前的流感疫苗在老年人中引发的免疫反应不如在年轻人中引发的反应强烈。迫切需要一种通用的流感病毒疫苗,能够在老年个体中诱导针对病毒感染的广泛保护性免疫。目前,针对多种流感病毒抗原上保守表位的流感病毒疫苗正在评估中。然而,几乎所有这些候选疫苗都是在成年动物模型中进行评估的。在本研究中,我们在对历史流感病毒具有预先免疫力的老年雪貂中评估了基于计算优化的广谱反应性抗原(COBRA)的流感疫苗,以评估疫苗诱导的保护性抗体反应的广度。用Infectimune®佐剂混合的COBRA血凝素(HA)和神经氨酸酶(NA)重组蛋白疫苗对老年雪貂进行接种,引发了针对疫苗中所有成分的强烈结合抗体。含有多种H3 COBRA HA成分的疫苗配方显著增强了针对H3N2病毒的血凝抑制(HAI)活性。此外,接种多价COBRA HA和NA疫苗的老年雪貂受到保护,免受感染,鼻病毒 shedding减少。总体而言,多价COBRA HA和NA疫苗可能是一种有效的疫苗策略,可降低老年人的发病率和死亡率。

相似文献

[1]
Multivalent H3 COBRA-based influenza vaccine elicits enhanced immune response in a pre-immune elderly ferret model.

Vaccine. 2025-5-22

[2]
Elicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza Viruses.

J Virol. 2019-1-17

[3]
A single dose of inactivated influenza virus vaccine expressing COBRA hemagglutinin elicits broadly-reactive and long-lasting protection.

PLoS One. 2025-2-21

[4]
Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses.

J Virol. 2017-11-30

[5]
Computationally Optimized Broadly Reactive Hemagglutinin Elicits Hemagglutination Inhibition Antibodies against a Panel of H3N2 Influenza Virus Cocirculating Variants.

J Virol. 2017-11-30

[6]
Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses.

mSphere. 2021-3-10

[7]
Intranasal administration of octavalent next-generation influenza vaccine elicits protective immune responses against seasonal and pre-pandemic viruses.

J Virol. 2024-9-17

[8]
Self-amplifying mRNA expressing COBRA hemagglutinin elicits long-lasting, broadly reactive antibodies against seasonal influenza A viruses.

Vaccine. 2025-7-4

[9]
Evaluation of Next-Generation H3 Influenza Vaccines in Ferrets Pre-Immune to Historical H3N2 Viruses.

Front Immunol. 2021

[10]
Multi-COBRA hemagglutinin formulated with cGAMP microparticles elicits protective immune responses against influenza viruses.

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引用本文的文献

[1]
Multivalent COBRA Hemagglutinin and Neuraminidase Influenza Vaccines Adjuvanted with TLR9 Agonist CpG 1018.

Vaccines (Basel). 2025-6-20

本文引用的文献

[1]
Computationally Optimized Hemagglutinin Proteins Adjuvanted with Infectimune Generate Broadly Protective Antibody Responses in Mice and Ferrets.

Vaccines (Basel). 2024-12-2

[2]
COBRA N2 NA vaccines induce protective immune responses against influenza viral infection.

Hum Vaccin Immunother. 2024-12-31

[3]
Longitudinal assessment of human antibody binding to hemagglutinin elicited by split-inactivated influenza vaccination over six consecutive seasons.

PLoS One. 2024

[4]
Inactivated influenza virus vaccines expressing COBRA hemagglutinin elicited broadly reactive, long-lived protective antibodies.

Hum Vaccin Immunother. 2024-12-31

[5]
mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020.

Front Immunol. 2024

[6]
Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age.

N Engl J Med. 2023-12-14

[7]
Systematic review of influenza vaccine effectiveness against laboratory-confirmed influenza among older adults living in aged care facilities.

Hum Vaccin Immunother. 2023-12-15

[8]
Cost effectiveness of quadrivalent influenza vaccines in the elderly population of Malaysia.

Sci Rep. 2023-10-31

[9]
A computationally optimized broadly reactive hemagglutinin vaccine elicits neutralizing antibodies against influenza B viruses from both lineages.

Sci Rep. 2023-9-23

[10]
Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice.

Sci Adv. 2023-9-15

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