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一种基于 ALVAC 载体的 RABV 病毒样颗粒候选疫苗在小鼠、猫和狗中单次给药可诱导强烈的免疫应答。

A single dose of an ALVAC vector-based RABV virus-like particle candidate vaccine induces a potent immune response in mice, cats and dogs.

机构信息

College of Veterinary Medicine, Jilin agricultural University, Changchun, People's Republic of China.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People's Republic of China.

出版信息

Emerg Microbes Infect. 2024 Dec;13(1):2406280. doi: 10.1080/22221751.2024.2406280. Epub 2024 Sep 30.


DOI:10.1080/22221751.2024.2406280
PMID:39295522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11443554/
Abstract

Rabies, caused by the Rabies virus (RABV), is a highly fatal zoonotic disease. Existing rabies vaccines have demonstrated good immune efficacy, but the complexity of immunization procedures and high cost has impeded the elimination of RABV, particularly in the post-COVID-19 era. There is a pressing need for safer and more effective rabies vaccines that streamline vaccination protocols and reduce expense. To meet this need, we have developed a potential rabies vaccine candidate called ALVAC-RABV-VLP, utilizing CRISPR/Cas9 gene editing technology. This vaccine employs a canarypox virus vector (ALVAC) to generate RABV virus-like particles (VLPs). In mice, a single dose of ALVAC-RABV-VLP effectively activated dendritic cells (DCs), follicular helper T cells (Tfh), and the germinal centre (GC)/plasma cell axis, resulting in durable and effective humoral immune responses. The survival rate of mice challenged with lethal RABV was 100%. Similarly, in dogs and cats, a single immunization with ALVAC-RABV-VLP elicited a stronger and longer-lasting antibody response. ALVAC-RABV-VLP induced superior cellular and humoral immunity in both mice and beagles compared to the commercial inactivated rabies vaccine. In conclusion, ALVAC-RABV-VLP induced robust protective immune responses in mice, dogs and cats, offering a novel, cost-effective, efficient, and promising approach for herd prevention of rabies.

摘要

狂犬病是由狂犬病病毒(Rabies virus,RABV)引起的一种高致死性的人畜共患病。现有的狂犬病疫苗已显示出良好的免疫效果,但免疫程序复杂且成本高昂,阻碍了 RABV 的消除,尤其是在 COVID-19 大流行之后。因此,迫切需要更安全、更有效的狂犬病疫苗,以简化疫苗接种方案并降低成本。为满足这一需求,我们利用 CRISPR/Cas9 基因编辑技术开发了一种名为 ALVAC-RABV-VLP 的潜在狂犬病疫苗候选物。该疫苗采用禽痘病毒载体(ALVAC)来产生 RABV 病毒样颗粒(VLPs)。在小鼠中,单次给予 ALVAC-RABV-VLP 可有效激活树突状细胞(DC)、滤泡辅助 T 细胞(Tfh)和生发中心(GC)/浆细胞轴,从而产生持久有效的体液免疫应答。接受致死性 RABV 攻击的小鼠的存活率为 100%。同样,在犬和猫中,单次免疫 ALVAC-RABV-VLP 可引起更强且更持久的抗体应答。与市售的狂犬病灭活疫苗相比,ALVAC-RABV-VLP 在小鼠和比格犬中诱导出更优的细胞和体液免疫。总之,ALVAC-RABV-VLP 可在小鼠、犬和猫中诱导出强大的保护性免疫应答,为狂犬病的群体预防提供了一种新颖、经济高效、有效的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/b53ec7b052c4/TEMI_A_2406280_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/7a654c92894d/TEMI_A_2406280_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/01328f7eca07/TEMI_A_2406280_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/6a20c613ef40/TEMI_A_2406280_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/83ac2e48cea4/TEMI_A_2406280_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/c7df61ffc89e/TEMI_A_2406280_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/25f446da75ce/TEMI_A_2406280_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/962393f52f7f/TEMI_A_2406280_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/b53ec7b052c4/TEMI_A_2406280_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/7a654c92894d/TEMI_A_2406280_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/01328f7eca07/TEMI_A_2406280_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/6a20c613ef40/TEMI_A_2406280_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/83ac2e48cea4/TEMI_A_2406280_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/c7df61ffc89e/TEMI_A_2406280_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/25f446da75ce/TEMI_A_2406280_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/962393f52f7f/TEMI_A_2406280_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16c7/11443554/b53ec7b052c4/TEMI_A_2406280_F0008_OC.jpg

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引用本文的文献

[1]
Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs.

PLoS One. 2025-5-12

本文引用的文献

[1]
A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum protection against SARS-CoV-2.

Antiviral Res. 2024-5

[2]
Transcriptome analysis of salivary glands of rabies-virus-infected mice.

Front Microbiol. 2024-2-6

[3]
A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs.

Emerg Microbes Infect. 2024-12

[4]
Virus-like particle vaccinology, from bench to bedside.

Cell Mol Immunol. 2022-9

[5]
Runx3 drives a CD8 T cell tissue residency program that is absent in CD4 T cells.

Nat Immunol. 2022-8

[6]
Letter to the editor: Safety and immunogenicity of a novel recombinant rabies vaccine.

Hum Vaccin Immunother. 2022-11-30

[7]
ALVAC-fIL2, a feline interleukin-2 immunomodulator, as a treatment for sarcoids in horses: A pilot study.

J Vet Intern Med. 2022-5

[8]
Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.

Nat Immunol. 2022-4

[9]
Safety and Immunogenicity of a novel three-dose recombinant nanoparticle rabies G protein vaccine administered as simulated post exposure immunization: A randomized, comparator controlled, multicenter, phase III clinical study.

Hum Vaccin Immunother. 2021-11-2

[10]
Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons.

Acta Neuropathol Commun. 2020-11-23

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