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异源初免-加强寨卡病毒疫苗接种在小鼠模型中诱导全面的体液免疫和细胞免疫。

Heterologous prime-boost Zika virus vaccination induces comprehensive humoral and cellular immunity in mouse models.

作者信息

De Lorenzo Giuditta, Tandavanitj Rapeepat, Preciado-Llanes Lorena, Sanchez-Velazquez Ricardo, Prado Rocha Raissa, Kim Young Chan, Reyes-Sandoval Arturo, Patel Arvind H

机构信息

MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.

Research and Technology Institute, Area Science Park, Trieste, Italy.

出版信息

Front Immunol. 2025 Apr 25;16:1578427. doi: 10.3389/fimmu.2025.1578427. eCollection 2025.

DOI:10.3389/fimmu.2025.1578427
PMID:40352923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12062147/
Abstract

Zika virus (ZIKV) remained poorly studied until an outbreak in 2015 linked the virus to severe neurological disorders and congenital malformations. Currently, there are no antiviral drugs or vaccines available. We have previously demonstrated that a simian adenovirus vector vaccine (ChAdOx1 prMEΔTM) and a virus-like particle-based vaccine bearing E proteins locked in covalent dimers (VLP-cvD) are effective against ZIKV infection in animal challenge models. In this study, we further explored the efficacy of these vaccines, either individually or in combination, using a heterologous prime and boost vaccination strategy in mouse challenge models. Although the individual vaccines provided good protection levels, the heterologous prime-boost vaccination regimen (ChAdOx1 prMEΔTM followed by VLP-cvD) offered the most effective protection. This regimen elicited a strong cellular response and high levels of neutralising antibodies, which were attributed to ChAdOx1 prMEΔTM and VLP-cvD, respectively. Our findings support the use of combined vaccine technologies and offer valuable insights into the multifactorial protection achievable through heterologous vaccination. These results have important implications for the development of effective vaccination strategies against ZIKV and other emerging viruses.

摘要

直到2015年爆发疫情,将寨卡病毒(ZIKV)与严重的神经疾病和先天性畸形联系起来,人们对该病毒的研究一直很少。目前,尚无可用的抗病毒药物或疫苗。我们之前已经证明,一种猿猴腺病毒载体疫苗(ChAdOx1 prMEΔTM)和一种基于病毒样颗粒的疫苗(其E蛋白以共价二聚体形式锁定,即VLP-cvD)在动物攻毒模型中对ZIKV感染有效。在本研究中,我们在小鼠攻毒模型中采用异源初免-加强免疫策略,进一步探究了这些疫苗单独使用或联合使用时的效果。尽管单独的疫苗提供了良好的保护水平,但异源初免-加强免疫方案(先接种ChAdOx1 prMEΔTM,随后接种VLP-cvD)提供了最有效的保护。该方案引发了强烈的细胞反应和高水平的中和抗体,分别归因于ChAdOx1 prMEΔTM和VLP-cvD。我们的研究结果支持联合疫苗技术的使用,并为通过异源接种可实现的多因素保护提供了有价值的见解。这些结果对开发针对ZIKV和其他新兴病毒的有效疫苗策略具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/e9d914389c0a/fimmu-16-1578427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/468e707833b0/fimmu-16-1578427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/63fc2a766c2c/fimmu-16-1578427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/b599dd24a326/fimmu-16-1578427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/e9d914389c0a/fimmu-16-1578427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/468e707833b0/fimmu-16-1578427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/63fc2a766c2c/fimmu-16-1578427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/b599dd24a326/fimmu-16-1578427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cfe/12062147/e9d914389c0a/fimmu-16-1578427-g004.jpg

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本文引用的文献

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Evaluation of an Engineered Zika Virus-Like Particle Vaccine Candidate in a Mosquito-Mouse Transmission Model.在蚊虫-鼠传播模型中评价一种工程化寨卡病毒样颗粒疫苗候选物。
mSphere. 2023 Apr 20;8(2):e0056422. doi: 10.1128/msphere.00564-22. Epub 2023 Feb 22.
2
Cellular Immunity-The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination.细胞免疫——从新冠病毒感染中康复及接种疫苗后个体长期保护的关键
Vaccines (Basel). 2022 Mar 14;10(3):442. doi: 10.3390/vaccines10030442.
3
The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.
黄病毒颗粒表面的表位排列有助于 Mab C10 对寨卡病毒和登革热病毒产生非凡的广谱中和作用。
Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub 2021 Nov 30.
4
Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial.腺病毒载体新冠疫苗和 mRNA 新冠疫苗序贯和同源加强接种的安全性和免疫原性比较(Com-COV):一项单盲、随机、非劣效性试验。
Lancet. 2021 Sep 4;398(10303):856-869. doi: 10.1016/S0140-6736(21)01694-9. Epub 2021 Aug 6.
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A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial.在一项 1 期临床试验中,单次接种 ChAdOx1 Chik 疫苗可诱导针对 4 种基孔肯雅病毒谱系的中和抗体。
Nat Commun. 2021 Jul 30;12(1):4636. doi: 10.1038/s41467-021-24906-y.
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Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data.异源初免-加强型新型冠状病毒肺炎疫苗接种:初始反应原性数据
Lancet. 2021 May 29;397(10289):2043-2046. doi: 10.1016/S0140-6736(21)01115-6. Epub 2021 May 12.
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J Virol. 2021 May 24;95(12). doi: 10.1128/JVI.00132-21.
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