Jaan Samavia, Zaman Aqal, Ahmed Sarfraz, Shah Mohibullah, Ojha Suvash Chandra
Department of Biochemistry, Bahauddin Zakariya University, Multan 66000, Pakistan.
Department of Microbiology & Molecular Genetics, Bahauddin Zakariya University, Multan 66000, Pakistan.
Vaccines (Basel). 2022 Sep 6;10(9):1476. doi: 10.3390/vaccines10091476.
Chikungunya virus is an alphavirus transmitted by mosquitos that develops into chikungunya fever and joint pain in humans. This virus' name originated from a Makonde term used to describe an illness that changes the joints and refers to the posture of afflicted patients who are affected by excruciating joint pain. There is currently no commercially available drug or vaccine for chikungunya virus infection and the treatment is performed by symptom reduction. Herein, we have developed a computationally constructed mRNA vaccine construct featuring envelope glycoprotein as the target molecule to aid in the treatment process. We have utilized the reverse vaccinology approach to determine epitopes that would generate adaptive immune reactions. The resulting T and B lymphocytes epitopes were screened by various immunoinformatic tools and a peptide vaccine construct was designed. It was validated by proceeding to docking and MD simulation studies. The following design was then back-translated in nucleotide sequence and codons were optimized according to the expression host system (). Various sequences, including 3' and 5' UTR regions, Kozak sequence, poly (A) tail, etc., were introduced into the sequence for the construction of the final mRNA vaccine construct. The secondary structure was generated for validation of the mRNA vaccine construct sequence. Additionally, in silico cloning was also performed to design a vector for proceeding towards in vitro experimentation. The proposed designed vaccine construct may proceed with experimental testing for further efficacy verification and the final development of a vaccine against chikungunya virus infection.
基孔肯雅病毒是一种由蚊子传播的甲病毒，可导致人类患上基孔肯雅热和关节疼痛。该病毒的名称源于一个 Makonde 术语，用于描述一种会影响关节的疾病，也指受极度关节疼痛影响的患者的姿势。目前，针对基孔肯雅病毒感染尚无商业化可用的药物或疫苗，治疗方式主要是减轻症状。在此，我们构建了一种通过计算设计的 mRNA 疫苗构建体，以包膜糖蛋白作为靶分子，辅助治疗过程。我们利用反向疫苗学方法来确定能够引发适应性免疫反应的表位。通过各种免疫信息学工具筛选得到的 T 淋巴细胞和 B 淋巴细胞表位，并设计了一种肽疫苗构建体。通过对接和分子动力学模拟研究对其进行了验证。然后将以下设计反向翻译成核苷酸序列，并根据表达宿主系统对密码子进行优化。为构建最终的 mRNA 疫苗构建体，将包括 3' 和 5' UTR 区域、科扎克序列、聚（A）尾等各种序列引入该序列。生成二级结构以验证 mRNA 疫苗构建体序列。此外，还进行了电子克隆以设计用于体外实验的载体。所提出的设计疫苗构建体可进行实验测试，以进一步验证疗效并最终开发出针对基孔肯雅病毒感染的疫苗。
