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单剂量复制子RNA苏丹病毒疫苗能一致地保护雌性豚鼠免受疾病侵害。

Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease.

作者信息

O'Donnell Kyle L, Anhalt Hanna, Saturday Greg, Warner Nikole L, Hinkley Troy, Stone E Taylor, Hatzakis Kiara, Khandhar Amit P, Banadyga Logan, Erasmus Jesse H, Marzi Andrea

机构信息

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

出版信息

Nat Commun. 2025 May 6;16(1):4199. doi: 10.1038/s41467-025-59560-1.

DOI:10.1038/s41467-025-59560-1
PMID:40328820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056027/
Abstract

The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV. We developed a SUDV vaccine candidate based on a nanocarrier (LION) complexed with an alphavirus-based replicon RNA. Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection. Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses correlate with decreased virus replication and survival. This result warrants further studies in larger animal species to ensure that protective efficacy is maintained with the single-dose LION-SUDV vaccine.

摘要

2022年和2025年苏丹病毒(SUDV)在乌干达爆发,引起了该国及整个东非地区的公共卫生担忧。目前尚无针对SUDV的获批对策。我们基于与基于甲病毒的复制子RNA复合的纳米载体(LION)开发了一种SUDV候选疫苗。在此,我们比较了单独编码SUDV糖蛋白(GP)或与埃博拉病毒(EBOV)GP联合编码的LION-SUDV疫苗的保护效果(LION组合疫苗)。还纳入了一种对EBOV有保护作用的LION-EBOV疫苗,以确定对SUDV感染的交叉保护潜力。使用雌性豚鼠疾病模型,在使用致死剂量的豚鼠适应型SUDV进行攻毒前三周进行单剂量疫苗接种。我们证明LION-SUDV疫苗和LION组合疫苗的存活率和保护率均为100%,而LION-EBOV疫苗的保护率为50%。抗原特异性体液反应与病毒复制减少和存活率相关。这一结果值得在更大的动物物种中进行进一步研究,以确保单剂量LION-SUDV疫苗能维持保护效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/0f411c2113e7/41467_2025_59560_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/bb77ae8470ad/41467_2025_59560_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/30b1f71627a6/41467_2025_59560_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/ee3e50546bdc/41467_2025_59560_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/0f411c2113e7/41467_2025_59560_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/bb77ae8470ad/41467_2025_59560_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/30b1f71627a6/41467_2025_59560_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/ee3e50546bdc/41467_2025_59560_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/12056027/0f411c2113e7/41467_2025_59560_Fig4_HTML.jpg

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本文引用的文献

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Nat Med. 2025 Feb 12. doi: 10.1038/d41591-025-00012-0.
2
Filovirus vaccines as a response paradigm for emerging infectious diseases.丝状病毒疫苗作为新兴传染病的应对范例。
NPJ Vaccines. 2024 Oct 11;9(1):186. doi: 10.1038/s41541-024-00985-y.
3
Packaging of alphavirus-based self-amplifying mRNA yields replication-competent virus through a mechanism of aberrant homologous RNA recombination.基于甲型病毒的自我扩增 mRNA 的包装通过异常同源 RNA 重组的机制产生复制型病毒。
mBio. 2024 Oct 16;15(10):e0249424. doi: 10.1128/mbio.02494-24. Epub 2024 Sep 25.
4
A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever.一种可复制的RNA疫苗在克里米亚-刚果出血热的恒河猴模型中提供保护。
NPJ Vaccines. 2024 May 20;9(1):86. doi: 10.1038/s41541-024-00887-z.
5
Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.安全性、免疫原性和疗效的自我扩增信使 RNA ARCT-154 COVID-19 疫苗:汇集阶段 1、2、3a 和 3b 随机、对照试验。
Nat Commun. 2024 May 14;15(1):4081. doi: 10.1038/s41467-024-47905-1.
6
An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial.一种针对奥密克戎的、自我扩增的 COVID-19 mRNA 加强疫苗:一项 2/3 期随机试验。
Nat Med. 2024 May;30(5):1363-1372. doi: 10.1038/s41591-024-02955-2. Epub 2024 Apr 18.
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Vaccines (Basel). 2024 Mar 17;12(3):318. doi: 10.3390/vaccines12030318.
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