背景:三种脑炎甲病毒-西方,东方,和委内瑞拉马脑炎病毒(WEEV,EEEV和VEEV)-可引起严重疾病,并有可能用作生物武器。没有批准的用于人类使用的疫苗。一种新的多价MVA-BN-WEV疫苗编码3种病毒的包膜表面蛋白,从而有可能对它们全部产生保护作用。正如先前在动物模型中所证明的那样。这项首次在人类中的研究评估了安全性,耐受性,MVA-BN-WEV疫苗在健康成人参与者中的免疫原性。
方法:将45名参与者纳入3个剂量组(1×10E7Inf。U,1×10E8Inf.U,和2×10E8Inf。U),相隔4周接受了2次剂量,然后监测6个月。
结果:MVA-BN-WEV的安全性在所有给药剂量下都是可接受的,随着剂量的增加,局部征询的AE的发生率增加,剂量组之间没有其他有临床意义的差异。在最低剂量组中报告了一个SAE(2级胸腔积液),并评估为可能相关。没有AE导致死亡或导致退出第二次疫苗接种或退出试验。最常见的局部诱发不良事件是注射部位疼痛,一般征询的AE是头痛,疲劳,和肌痛。MVA-BN-WEV诱导的体液免疫反应;WEEV-,EEEV和VEEV特异性中和抗体反应在第二次疫苗接种后2周达到峰值,这些反应的幅度随着剂量的增加而增加。最高剂量导致WEEV和VEEV的所有(100%)参与者的血清转化,EEEV的92.9%,第二次接种疫苗后2周,并观察到6个月的耐久性。MVA-BN-WEV诱导对VEEVE1和E2的细胞免疫应答(EEEV和WEEV未测试)和肽库E2的剂量效应。
结论:研究表明MVA-BN-WEV具有良好的耐受性,诱导免疫反应,适合进一步发展。
背景:NCT04131595。
BACKGROUND: Three encephalitic alphaviruses-western, eastern, and Venezuelan equine encephalitis virus (WEEV, EEEV and VEEV)-can cause severe disease and have the potential to be used as biological weapons. There are no approved vaccines for human use. A novel multivalent MVA-BN-WEV vaccine encodes the envelope surface proteins of the 3 viruses and is thereby potentially able to protect against them all, as previously demonstrated in animal models. This first-in-human study assessed the safety, tolerability, and immunogenicity of MVA-BN-WEV vaccine in healthy adult participants.
METHODS: Forty-five participants were enrolled into 3 dose groups (1 × 10E7 Inf.U, 1 × 10E8 Inf.U, and 2 × 10E8 Inf.U), received 2 doses 4 weeks apart, and were then monitored for 6 months.
RESULTS: The safety profile of MVA-BN-WEV was acceptable at all administered doses, with incidence of local solicited AEs increased with increasing dose and no other clinically meaningful differences between dose groups. One SAE (Grade 2 pleural effusion) was reported in the lowest dose group and assessed as possibly related. No AEs resulted in death or led to withdrawal from the second vaccination or from the trial. The most common local solicited AE was injection site pain, and general solicited AEs were headache, fatigue, and myalgia. MVA-BN-WEV induced humoral immune responses; WEEV-, EEEV- and VEEV-specific neutralizing antibody responses peaked 2 weeks following the second vaccination, and the magnitude of these responses increased with dose escalation. The highest dose resulted in seroconversion of all (100 %) participants for WEEV and VEEV and 92.9 % for EEEV, 2 weeks following second vaccination, and durability was observed for 6 months. MVA-BN-WEV induced cellular immune responses to VEEV E1 and E2 (EEEV and WEEV not tested) and a dose effect for peptide pool E2.
CONCLUSIONS: The study demonstrated that MVA-BN-WEV is well tolerated, induces immune responses, and is suitable for further development.
BACKGROUND: NCT04131595.