Shrivastava Neha, Verma Ankit, Dash Paban Kumar
Division of Virology, Defence Research and Development Establishment, Jhansi Road, Gwalior, PIN-474002, India.
Division of Virology, Defence Research and Development Establishment, Jhansi Road, Gwalior, PIN-474002, India.
Eur J Pharm Sci. 2020 Aug 1;151:105396. doi: 10.1016/j.ejps.2020.105396. Epub 2020 May 30.
Recurrent outbreaks of Crimean-Congo hemorrhagic fever (CCHF) virus infection in different parts of world are a major global health concern. The CCHF viral infection is associated with severe hemorrhagic fevers and mortality up to 40%. More than 30 countries in Asia, Europe and Africa are affected with CCHF infection. Prevention of infection through vaccine becomes more important when no effective antiviral and associated therapies are available. Further ticks play a crucial role in maintenance and transmission of CCHFV. Therefore, the control of transmission by ticks is warranted for ultimate prevention of outbreak. The study employed a series of immunoinformatics approaches to design novel multiepitope vaccine targeting highly immunodominant epitopes of major structural proteins (Nucleoprotein and Glycoprotein complex) of CCHFV. Vaccine was designed by incorporating linear and conformational B cell, helper and cytotoxic T cell epitopes from these crucial immunogenic proteins adjoined with appropriate linkers and adjuvant. This vaccine construct was also complemented with a highly immunogenic and conserved protective tick salivary antigen named subolesin to impart dual activity as a unique transmission blocking vaccine. The B-cell peptides were also experimentally validated. The designed vaccine was further in silico validated for its physiochemical properties, allergenicity and immunogenicity etc. The proposed candidate vaccine construct has the potential to function both as a vaccine against CCHF virus as well as a universal anti-tick vaccine.
克里米亚-刚果出血热(CCHF)病毒感染在世界不同地区反复爆发,是全球主要的健康问题。CCHF病毒感染与严重出血热相关,死亡率高达40%。亚洲、欧洲和非洲的30多个国家受到CCHF感染影响。在没有有效的抗病毒药物及相关治疗方法的情况下,通过疫苗预防感染变得更加重要。此外,蜱虫在CCHFV的维持和传播中起着关键作用。因此,有必要控制蜱虫传播以最终预防疫情爆发。该研究采用了一系列免疫信息学方法,设计针对CCHFV主要结构蛋白(核蛋白和糖蛋白复合物)高度免疫显性表位的新型多表位疫苗。通过整合来自这些关键免疫原性蛋白的线性和构象性B细胞、辅助性和细胞毒性T细胞表位,并连接适当的接头和佐剂来设计疫苗。该疫苗构建体还补充了一种名为亚油酸结合蛋白的高度免疫原性且保守的保护性蜱唾液抗原,以作为一种独特的传播阻断疫苗发挥双重作用。B细胞肽也经过了实验验证。设计的疫苗还通过计算机模拟对其理化性质、致敏性和免疫原性等进行了验证。所提出的候选疫苗构建体有潜力既作为针对CCHF病毒的疫苗,又作为通用的抗蜱疫苗发挥作用。