Globally, ~20% of cancer malignancies are associated with virus infections. Lung cancer is the most prevalent cancer and has a 10% 5-year survival rate when diagnosed at stage IV. Cancer vaccines and oncolytic immunotherapy are promising treatment strategies for better clinical outcomes in advanced-stage cancer patients. Here, we used a reverse vaccinology approach to devise subunit vaccine candidates against lung cancer-causing oncogenic viruses. Protein components (945) from nine oncogenic virus species were systematically analyzed to identify epitope-based subunit vaccine candidates. Best vaccine candidates were identified based on their predicted ability to stimulate humoral and cell-mediated immunity and avoid self-tolerance. Using a rigorous integrative approach, we identified 125 best antigenic epitopes with predicted B-cell, T-cell, and/or MHC-binding capability and vaccine adjuvant potential. Thirty-two of these antigenic epitopes were predicted to have IL-4/IFN-gamma inducing potential and IL-10 non-inducing potential and were predicted to bind 15 MHC-type I and 49 MHC-type II alleles. All 32 epitopes were non-allergenic and 31 were non-toxic. The identified epitopes showed good conservancy and likely bind a broad class of human HLA alleles, indicating promiscuous potential. The majority of best antigenic epitopes were derived from Human papillomavirus and Epstein-Barr virus proteins. Of the 32 epitopes, 25 promiscuous epitopes were related to E1 and E6 envelope genes and were present in multiple viral strains/species, potentially providing heterologous immunity. Further validating our results, 38 antigenic epitopes were also present in the largest experimentally-validated epitope resource, Immune Epitope Database and Analysis Resource. We further narrowed the selection to 29 antigenic epitopes with the highest immunogenic/immune-boosting potential. These epitopes possess tremendous therapeutic potential as vaccines against lung cancer-causing viruses and should be validated in future experiments. All findings are available at https://webs.iiitd.edu.in/raghava/vlcvirus/.

在全球范围内，约20％的恶性肿瘤与病毒感染有关。肺癌是最普遍的癌症，在IV期被诊断出时，其5年生存率达到10％。癌症疫苗和溶瘤免疫疗法是有望在晚期癌症患者中取得更好临床效果的治疗策略。在这里，我们使用了反向疫苗学方法来设计针对致癌致癌病毒的亚单位候选疫苗。系统分析了来自九种致癌病毒物种的蛋白质成分（945），以鉴定基于表位的亚基疫苗候选物。根据其预期的刺激体液和细胞介导的免疫力并避免自我耐受的能力，确定最佳的候选疫苗。使用严格的整合方法，我们确定了125种最佳抗原表位，它们具有预测的B细胞，T细胞，和/或MHC结合能力和疫苗佐剂的潜力。这些抗原表位中的32个被预测具有IL-4 /IFN-γ诱导潜能和IL-10非诱导潜能，并被预测与15个MHC I型和49个MHC II型等位基因结合。所有32个表位均为非过敏性，31个为无毒。鉴定出的表位显示出良好的保守性，并可能结合广泛的人类HLA等位基因，显示出混杂的潜力。大多数最佳抗原表位来自 鉴定出的表位显示出良好的保守性，并可能结合广泛的人类HLA等位基因，显示出混杂的潜力。大多数最佳抗原表位来自 鉴定出的表位显示出良好的保守性，并可能结合广泛的人类HLA等位基因，表明可能存在混杂现象。大多数最佳抗原表位来自人乳头瘤病毒和爱泼斯坦-巴尔病毒蛋白。在这32个表位中，有25个混杂表位与E1和E6包膜基因有关，并存在于多种病毒株/物种中，可能提供异源免疫。为了进一步验证我们的结果，在最大的实验验证表位资源，免疫表位数据库和分析资源中也存在38个抗原表位。我们进一步将选择范围缩小到具有最高免疫原性/免疫增强潜能的29个抗原表位。这些表位具有巨大的治疗潜力，可作为抗肺癌病毒的疫苗，应在以后的实验中进行验证。所有发现均可在https://webs.iiitd.edu.in/raghava/vlcvirus/中找到。