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In-silico identification of subunit vaccine candidates against lung cancer-associated oncogenic viruses

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title In-silico identification of subunit vaccine candidates against lung cancer-associated oncogenic viruses
 
Creator Lathwal, Anjali
Kumar, Rajesh
Raghava, Gajendra P. S.
 
Subject QR Microbiology
 
Description 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
 
Publisher Elsevier
 
Date 2021-03
 
Type Article
PeerReviewed
 
Relation https://www.sciencedirect.com/science/article/abs/pii/S0010482521000093?via%3Dihub
http://crdd.osdd.net/open/2740/
 
Identifier Lathwal, Anjali and Kumar, Rajesh and Raghava, Gajendra P. S. (2021) In-silico identification of subunit vaccine candidates against lung cancer-associated oncogenic viruses. COMPUTERS IN BIOLOGY AND MEDICINE, 130.