Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan 60800, Pakistan.
School of Information and Technology, Wenzhou Business College, Wenzhou 325015, China.
Molecules. 2023 Feb 10;28(4):1687. doi: 10.3390/molecules28041687.
Human papilloma virus (HPV) causes cervical and many other cancers. Recent trend in vaccine design is shifted toward epitope-based developments that are more specific, safe, and easy to produce. In this study, we predicted eight immunogenic peptides of CD4+ and CD8+ T-lymphocytes (MHC class I and II as M1 and M2) including early proteins (E2 and E6), major (L1) and minor capsid protein (L2). Male and female Sprague Dawly rats in groups were immunized with each synthetic peptide. L1M1, L1M2, L2M1, and L2M2 induced significant immunogenic response compared to E2M1, E2M2, E6M1 and E6M2. We observed optimal titer of IgG antibodies (>1.25 g/L), interferon-γ (>64 ng/L), and granzyme-B (>40 pg/mL) compared to control at second booster dose (240 µg/500 µL). The induction of peptide-specific IgG antibodies in immunized rats indicates the T-cell dependent B-lymphocyte activation. A substantial CD4+ and CD8+ cell count was observed at 240 µg/500 µL. In male and female rats, CD8+ cell count for L1 and L2 peptide is 3000 and 3118, and CD4+ is 3369 and 3484 respectively compared to control. In conclusion, we demonstrated that L1M1, L1M2, L2M1, L2M2 are likely to contain potential epitopes for induction of immune responses supporting the feasibility of peptide-based vaccine development for HPV.
人乳头瘤病毒 (HPV) 可导致宫颈癌和许多其他癌症。最近疫苗设计的趋势转向基于表位的开发，这种方法更具特异性、安全性且易于生产。在这项研究中，我们预测了 8 种针对 CD4+和 CD8+T 淋巴细胞（MHC Ⅰ类和Ⅱ类作为 M1 和 M2）的免疫原性肽，包括早期蛋白 (E2 和 E6)、主要 (L1) 和次要衣壳蛋白 (L2)。雄性和雌性 Sprague Dawly 大鼠分组用每种合成肽免疫。与 E2M1、E2M2、E6M1 和 E6M2 相比，L1M1、L1M2、L2M1 和 L2M2 诱导了显著的免疫应答。与对照组相比，在第二次加强剂量（240µg/500µL）时，我们观察到 IgG 抗体（>1.25g/L）、干扰素-γ（>64ng/L）和颗粒酶-B（>40pg/mL）的最佳效价。免疫大鼠中肽特异性 IgG 抗体的诱导表明 T 细胞依赖 B 淋巴细胞的激活。在 240µg/500µL 时观察到 CD4+和 CD8+细胞计数显著增加。在雄性和雌性大鼠中，L1 和 L2 肽的 CD8+细胞计数分别为 3000 和 3118，CD4+分别为 3369 和 3484，与对照组相比。总之，我们证明 L1M1、L1M2、L2M1、L2M2 可能含有诱导免疫反应的潜在表位，支持 HPV 基于肽的疫苗开发的可行性。
