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评估编码呼吸道合胞病毒融合蛋白（RSV-F）的腺病毒载体Ad19a作为抗呼吸道合胞病毒新型疫苗的效果。

Evaluation of adenoviral vector Ad19a encoding RSV-F as novel vaccine against respiratory syncytial virus.

作者信息

Fuchs Jana, Hübner Julian, Schmidt Anna, Irrgang Pascal, Maier Clara, Vieira Antão Ana, Oltmanns Friederike, Thirion Christian, Lapuente Dennis, Tenbusch Matthias

机构信息

Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany.

Sirion Biotech, Am Klopferspitz 19, 82152, Martinsried, Germany.

出版信息

NPJ Vaccines. 2024 Oct 29;9(1):205. doi: 10.1038/s41541-024-01001-z.

DOI:10.1038/s41541-024-01001-z
PMID:39472590
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11522487/
Abstract

Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in infants and toddlers. Since natural infections do not induce persistent immunity, there is the need of vaccines providing long-term protection. Here, we evaluated a new adenoviral vector (rAd) vaccine based on the rare serotype rAd19a and compared the immunogenicity and efficacy to the highly immunogenic rAd5. Given as an intranasal boost in DNA primed mice, both vectors encoding the F protein provided efficient protection against a subsequent RSV infection. However, intramuscular immunization with rAd19a vectors provoked vaccine-enhanced disease after RSV infection compared to non-vaccinated animals. While mucosal IgA antibodies and tissue-resident memory T-cells in intranasally vaccinated mice rapidly control RSV replication, a strong anamnestic systemic T-cell response in absence of local immunity might be the reason for immune-mediated enhanced disease. Our study highlighted the potential benefits of developing effective mucosal against respiratory pathogens.

摘要

呼吸道合胞病毒（RSV）是婴幼儿严重下呼吸道感染的主要病因。由于自然感染不会诱导持久免疫力，因此需要能提供长期保护的疫苗。在此，我们评估了一种基于罕见血清型rAd19a的新型腺病毒载体（rAd）疫苗，并将其免疫原性和效力与高免疫原性的rAd5进行了比较。在经DNA预免疫的小鼠中进行鼻内加强免疫后，两种编码F蛋白的载体均能有效保护小鼠免受随后的RSV感染。然而，与未接种疫苗的动物相比，用rAd19a载体进行肌肉内免疫会在RSV感染后引发疫苗增强型疾病。虽然鼻内接种疫苗的小鼠中的黏膜IgA抗体和组织驻留记忆T细胞能迅速控制RSV复制，但在缺乏局部免疫的情况下强烈的回忆性全身T细胞反应可能是免疫介导的疾病增强的原因。我们的研究突出了开发针对呼吸道病原体的有效黏膜疫苗的潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/c1f2fa22f7d8/41541_2024_1001_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/71cbecf2c6a1/41541_2024_1001_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/c1f2fa22f7d8/41541_2024_1001_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/71cbecf2c6a1/41541_2024_1001_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/0be4667899e9/41541_2024_1001_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/fe6f4d4349d3/41541_2024_1001_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/8373aa0c2133/41541_2024_1001_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/7ebef5b1fec7/41541_2024_1001_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/2bd9575cda58/41541_2024_1001_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/2ae068b95763/41541_2024_1001_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/d0dc47ff78eb/41541_2024_1001_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/3ae8a9b6166b/41541_2024_1001_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/f919f6e66e8b/41541_2024_1001_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4550/11522487/c1f2fa22f7d8/41541_2024_1001_Fig11_HTML.jpg

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