Pandey Rajan Kumar, Ojha Rupal, Dipti Kumari, Kumar Rajiv, Prajapati Vijay Kumar
Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Near NH-8, Bandarsindri, 305817, Kishangarh, Ajmer, Rajasthan, India.
Department of Bioscience and Biotechnology, Bansthali Vidyapith, Jaipur, Rajasthan 304022, India.
Infect Genet Evol. 2020 Aug;82:104282. doi: 10.1016/j.meegid.2020.104282. Epub 2020 Mar 10.
Human cytomegalovirus (HCMV) generally causes asymptomatic infection, but sometimes it may cause severe complications among immunocompromised individuals. It may also promote various malignancies like prostate cancer and breast cancer. However, even after having this severe illness, there is no effective cure yet. This situation urges the need for effective chemotherapeutics or vaccination to tackle this severe complication.
A combinatorial screening algorithm was applied to design a subunit vaccine consisting of B-cell epitopes, CTL- and HTL epitopes along with a suitable adjuvant (TLR-4 agonist) and linkers. The conservancy of CTL, HTL, and B-cell epitopes was also determined. Further, physicochemical characterization, antigenicity, and allergenicity were determined to check the safety and immunogenic behavior of the designed vaccine candidate. Later on, the 3D structure of the vaccine protein was determined, followed by molecular docking and molecular dynamics simulation with TLR-4 to check their binding free energy and complex stability.
A subunit vaccine of 964 amino acid residues was developed, having good immunogenicity and non-allergenicity behavior. The designed subunit vaccine has HTL epitopes with their ability to induce the release of IFN-γ cytokine. The sorted HTL and CTL epitopes were found to be conserved among two available strains of HCMV. It has also shown an excellent binding affinity with the TLR-4 receptor along with the formation of the stable complex as determined by a molecular dynamics simulation study.
The designed subunit vaccine may have the ability to induce an immunogenic response and memory cell formation to protect against the HCMV mediated disease conditions.
人巨细胞病毒（HCMV）通常引起无症状感染，但有时可能在免疫功能低下的个体中导致严重并发症。它还可能促进各种恶性肿瘤，如前列腺癌和乳腺癌。然而，即使患有这种严重疾病，目前仍没有有效的治愈方法。这种情况促使需要有效的化疗药物或疫苗来应对这种严重并发症。
应用组合筛选算法设计一种亚单位疫苗，该疫苗由B细胞表位、CTL和HTL表位以及合适的佐剂（TLR-4激动剂）和连接子组成。还确定了CTL、HTL和B细胞表位的保守性。此外，测定了物理化学特性、抗原性和致敏性，以检查所设计疫苗候选物的安全性和免疫原性。随后，确定了疫苗蛋白的三维结构，接着与TLR-4进行分子对接和分子动力学模拟，以检查它们的结合自由能和复合物稳定性。
开发了一种由964个氨基酸残基组成的亚单位疫苗，具有良好的免疫原性和非致敏性。所设计的亚单位疫苗具有HTL表位，能够诱导IFN-γ细胞因子的释放。发现分选的HTL和CTL表位在两种可用的HCMV毒株中是保守的。分子动力学模拟研究表明，它与TLR-4受体也具有优异的结合亲和力，并形成稳定的复合物。
所设计的亚单位疫苗可能具有诱导免疫原性反应和记忆细胞形成的能力，以预防HCMV介导的疾病状况。
