Wang Danher, Raja Nicholas U, Trubey Charles M, Juompan Laure Y, Luo Min, Woraratanadharm Jan, Deitz Stephen B, Yu Hong, Swain Benjamin M, Moore Kevin M, Pratt William D, Hart Mary Kate, Dong John Y
Division of Biodefense Vaccines, GenPhar, Inc., 871 Lowcountry Blvd., Mount Pleasant, South Carolina 29464, USA.
J Virol. 2006 Mar;80(6):2738-46. doi: 10.1128/JVI.80.6.2738-2746.2006.
Ebola virus (EBOV) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. While lethal human outbreaks have so far been restricted to sub-Saharan Africa, the potential exploitation of EBOV as a biological weapon cannot be ignored. Two species of EBOV, Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV), have been responsible for all of the deadly human outbreaks resulting from this virus. Therefore, it is important to develop a vaccine that can prevent infection by both lethal species. Here, we describe the bivalent cAdVaxE(GPs/z) vaccine, which includes the SEBOV glycoprotein (GP) and ZEBOV GP genes together in a single complex adenovirus-based vaccine (cAdVax) vector. Vaccination of mice with the bivalent cAdVaxE(GPs/z) vaccine led to efficient induction of EBOV-specific antibody and cell-mediated immune responses to both species of EBOV. In addition, the cAdVax technology demonstrated induction of a 100% protective immune response in mice, as all vaccinated C57BL/6 and BALB/c mice survived challenge with a lethal dose of ZEBOV (30,000 times the 50% lethal dose). This study demonstrates the potential efficacy of a bivalent EBOV vaccine based on a cAdVax vaccine vector design.
埃博拉病毒(EBOV)可引发严重的出血热,目前尚无针对该病毒的疫苗或有效治疗方法。尽管迄今为止致命的人类疫情仅局限于撒哈拉以南非洲地区,但埃博拉病毒被用作生物武器的潜在威胁不容忽视。埃博拉病毒的两个物种,即苏丹埃博拉病毒(SEBOV)和扎伊尔埃博拉病毒(ZEBOV),引发了该病毒导致的所有致命人类疫情。因此,研发一种能够预防这两种致命病毒感染的疫苗至关重要。在此,我们描述了二价cAdVaxE(GPs/z)疫苗,它将SEBOV糖蛋白(GP)和ZEBOV GP基因共同整合在一个基于复合腺病毒的疫苗(cAdVax)载体中。用二价cAdVaxE(GPs/z)疫苗对小鼠进行免疫接种,能够有效诱导针对两种埃博拉病毒的埃博拉病毒特异性抗体和细胞介导的免疫反应。此外,cAdVax技术在小鼠中诱导出了100%的保护性免疫反应,因为所有接种疫苗的C57BL/6和BALB/c小鼠在接受致死剂量的ZEBOV(50%致死剂量的30,000倍)攻击后均存活下来。这项研究证明了基于cAdVax疫苗载体设计的二价埃博拉病毒疫苗的潜在有效性。