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基于改良痘苗病毒安卡拉(MVA)的疫苗可保护食蟹猕猴免受东部马脑炎病毒气溶胶攻击致死。

MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques.

作者信息

Beddingfield Brandon J, Plante Kenneth S, Plante Jessica A, Weaver Scott C, Bose Sarah, Krzykwa Clara, Chirichella Nicole, Redmann Rachel K, Seiler Stephanie Z, Dufour Jason, Blair Robert V, Endt Kathrin, Volkmann Ariane, Maness Nicholas J, Roy Chad J

机构信息

Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

出版信息

NPJ Vaccines. 2024 Feb 27;9(1):47. doi: 10.1038/s41541-024-00842-y.

DOI:10.1038/s41541-024-00842-y
PMID:38413593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10899228/
Abstract

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 10 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 10 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

摘要

在食蟹猴气溶胶感染东部马脑炎病毒(EEEV)模型中评估了基于改良痘苗病毒安卡拉(MVA)的单价东部马脑炎病毒疫苗(MVA-BN-EEEV)和多价西部、东部及委内瑞拉马脑炎病毒疫苗(MVA-BN-WEV)。通过肌肉注射途径用两剂5×10感染单位的MVA-BN-EEEV或MVA-BN-WEV疫苗接种的食蟹猴,迅速产生了针对EEEV的高效中和抗体水平,这些抗体水平在第84天通过小颗粒气溶胶递送、目标吸入剂量为10 PFU的EEEV FL93-939进行攻击之前一直保持在高水平。观察到了强大的保护作用,接受MVA-BN-EEEV的8只动物中有7只存活,接受MVA-BN-WEV的动物100%(8/8)存活,而仅接种安慰剂的对照组8只动物中只有2只在致死性攻击中存活。两种疫苗都提供了完全的病毒血症保护,对组织中的病毒RNA载量以及中枢神经系统损伤的任何病理证据提供了近乎完全的保护。总体而言,结果表明两种疫苗在引发免疫反应方面都是有效的,这种免疫反应与免受气溶胶化EEEV诱导疾病的保护作用一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/07eabbe1979f/41541_2024_842_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/b774e87262b6/41541_2024_842_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/dd61b6e83944/41541_2024_842_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/569545fd445a/41541_2024_842_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/d07996a56659/41541_2024_842_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/07eabbe1979f/41541_2024_842_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/b774e87262b6/41541_2024_842_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/dd61b6e83944/41541_2024_842_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/569545fd445a/41541_2024_842_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/d07996a56659/41541_2024_842_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a1b/10899228/07eabbe1979f/41541_2024_842_Fig5_HTML.jpg

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