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黏膜二价减毒活疫苗可保护小鼠免受人偏肺病毒和呼吸道合胞病毒感染。

Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice.

作者信息

Ogonczyk-Makowska Daniela, Brun Pauline, Vacher Clémence, Chupin Caroline, Droillard Clément, Carbonneau Julie, Laurent Emilie, Dulière Victoria, Traversier Aurélien, Terrier Olivier, Julien Thomas, Galloux Marie, Paul Stéphane, Eléouët Jean-François, Fouret Julien, Hamelin Marie-Eve, Pizzorno Andrés, Boivin Guy, Rosa-Calatrava Manuel, Dubois Julia

机构信息

Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Québec, QC, G1V 4G2, Canada.

International Research Laboratory RESPIVIR France - Canada, Centre de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, 69008, Lyon, France, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de Lyon, France, Centre Hospitalier Universitaire de Québec - Université Laval, QC G1V 4G2, Québec, Canada.

出版信息

NPJ Vaccines. 2024 Jun 19;9(1):111. doi: 10.1038/s41541-024-00899-9.

DOI:10.1038/s41541-024-00899-9
PMID:38898106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11187144/
Abstract

Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.

摘要

减毒活疫苗（LAVs）可刺激强烈的黏膜和细胞反应，有潜力预防呼吸道合胞病毒（RSV）和人偏肺病毒（HMPV），这两种病毒是儿童病毒性细支气管炎和肺炎的主要病原体。我们将RSV-F基因插入到一种基于HMPV的减毒活疫苗（Metavac®）中，该疫苗我们之前已验证可保护小鼠免受HMPV攻击，并拯救出一种复制性重组病毒（Metavac®-RSV），其在病毒粒子表面同时暴露RSV和HMPV-F蛋白，并在重建的人气道上皮模型中表达。当通过鼻内途径给予BALB/c小鼠时，二价Metavac®-RSV显示出其在降低肺部炎症评分的情况下进行复制的能力，并能保护接种疫苗的小鼠免受RSV和致死性HMPV攻击，同时诱导强烈的IgG以及广泛的RSV和HMPV中和抗体反应。总之，我们的结果显示了Metavac®平台的多功能性，并表明Metavac®-RSV是一种有前景的黏膜二价减毒活疫苗候选物，可预防肺病毒引起的疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/b7b7a528eee2/41541_2024_899_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/5566292ce864/41541_2024_899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/f68e0d493867/41541_2024_899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/28cb05b39573/41541_2024_899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/718bf1158d8e/41541_2024_899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/6834674e2790/41541_2024_899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/28f4d0685784/41541_2024_899_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/b7b7a528eee2/41541_2024_899_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/5566292ce864/41541_2024_899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/f68e0d493867/41541_2024_899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/28cb05b39573/41541_2024_899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/718bf1158d8e/41541_2024_899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/6834674e2790/41541_2024_899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/28f4d0685784/41541_2024_899_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f46/11187144/b7b7a528eee2/41541_2024_899_Fig7_HTML.jpg

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引用本文的文献

[1]
Evaluating the efficacy, safety, and immunogenicity of FDA-approved RSV vaccines: a systematic review of Arexvy, Abrysvo, and mResvia.

Front Immunol. 2025-8-18

[2]
Human Metapneumovirus: A Narrative Review on Emerging Strategies for Prevention and Treatment.

Viruses. 2025-8-20

[3]
Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor.

NPJ Vaccines. 2025-8-22

[4]
hMPV Outbreaks: Worldwide Implications of a Re-Emerging Respiratory Pathogen.

Microorganisms. 2025-6-27

[5]
Vaccine Development for Human Pneumoviruses.

Vaccines (Basel). 2025-5-26

[6]
Innovations, Challenges, and Future Prospects for Combination Vaccines Against Human Infections.

Vaccines (Basel). 2025-3-21

[7]
Recent advances in the prevention and treatment of respiratory syncytial virus disease.

J Gen Virol. 2025-4

[8]
Generation of nanobodies against the F protein of respiratory syncytial virus and establishment of an indirect immunofluorescence assay.

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本文引用的文献

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