Single-dose VSV-based vaccine protects cynomolgus macaques from disease after Taï Forest virus infection.
Single-dose VSV-based vaccine protects cynomolgus macaques from disease after Taï Forest virus infection.
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DOI：
10.1080/22221751.2023.2239950
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发表时间：
2023-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
塔霍河森林病毒（TAFV）是一种鲜为人知的埃博拉病毒，可导致黑猩猩致命感染，并导致一例人类病例。对这种人类病原体的研究有限;然而，随着西非最近出现丝状病毒，有必要对这种病毒进行进一步调查和制定对策。我们开发了一种基于水泡性口炎病毒（VSV）的疫苗，表达TAFV糖蛋白作为病毒抗原，并评估了其在非人灵长类动物（NHP）中的保护效力。在单次高剂量疫苗接种后，NHP产生抗原特异性结合和中和抗体以及适度的T细胞应答。重要的是，在致死性TAFV攻击后，所有接种疫苗的NHP均受到保护，而未接种疫苗的对照组死于疾病。与丝状病毒病一致的组织学病变存在于对照NHP中，但在接种疫苗的NHP中未观察到。对接种疫苗和攻毒后获得的全血样本进行转录分析，以深入了解提供保护的分子基础。在接种疫苗后7天检测到的差异表达基因（DEG）富集到与先天免疫和抗病毒应答相关的过程。在攻击后接种疫苗的NHP中仅检测到少量DEG，而在疾病末期的对照NHP中检测到超过1，000个DEG，其映射到指示防御反应和炎症的基因本体术语。综上所述，这些数据表明VSV-TAFV疫苗的有效单剂量保护作用及其在暴发中使用的潜力。
Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been done on this human pathogen; however, with the recent emergence of filoviruses in West Africa, further investigation and countermeasure development against this virus is warranted. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the TAFV glycoprotein as the viral antigen and assessed it for protective efficacy in nonhuman primates (NHPs). Following a single high-dose vaccination, NHPs developed antigen-specific binding and neutralizing antibodies as well as modest T cell responses. Importantly, all vaccinated NHPs were uniformly protected from disease after lethal TAFV challenge while the naïve control group succumbed to the disease. Histopathologic lesions consistent with filovirus disease were present in control NHPs but were not observed in vaccinated NHPs. Transcriptional analysis of whole blood samples obtained after vaccination and challenge was performed to gain insight into molecular underpinnings conferring protection. Differentially expressed genes (DEG) detected 7 days post-vaccination were enriched to processes associated with innate immunity and antiviral responses. Only a small number of DEG was detected in vaccinated NHPs post-challenge while over 1,000 DEG were detected in control NHPs at end-stage disease which mapped to gene ontology terms indicative of defense responses and inflammation. Taken together, this data demonstrates the effective single-dose protection of the VSV-TAFV vaccine, and its potential for use in outbreaks.
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DOI：
10.3390/pathogens9100850
发表时间：
2020-10-17
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Jain S;Khaiboullina SF;Baranwal M
通讯作者：
Baranwal M
影响因子：
3.3
作者：
Feldmann, Friederike;Shupert, W. Lesley;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
8.8
作者：
Marzi, Andrea;Chadinah, Spencer;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
11.1
作者：
Marzi, Andrea;Reynolds, Pierce;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
DOI：
10.1016/s1473-3099(18)30165-8
发表时间：
2018-07
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Huttner A;Agnandji ST;Combescure C;Fernandes JF;Bache EB;Kabwende L;Ndungu FM;Brosnahan J;Monath TP;Lemaître B;Grillet S;Botto M;Engler O;Portmann J;Siegrist D;Bejon P;Silvera P;Kremsner P;Siegrist CA;VEBCON;VSV-EBOVAC;VSV-EBOPLUS Consortia
通讯作者：
VSV-EBOPLUS Consortia