Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here,...

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Main Authors: Jiani Chen, Swan Tan, Vasanthi Avadhanula, Leonard Moise, Pedro A Piedra, Anne S De Groot, Justin Bahl
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1010360
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author Jiani Chen
Swan Tan
Vasanthi Avadhanula
Leonard Moise
Pedro A Piedra
Anne S De Groot
Justin Bahl
author_facet Jiani Chen
Swan Tan
Vasanthi Avadhanula
Leonard Moise
Pedro A Piedra
Anne S De Groot
Justin Bahl
author_sort Jiani Chen
collection DOAJ
description Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally validated. We applied multidimensional scaling (MDS) to construct T cell epitope landscapes to investigate the diversity and evolution of T cell profiles across different RSV strains. We find the RSV strains are clustered into three RSV-A groups and two RSV-B groups on this T epitope landscape. These clusters represent divergent RSV strains with potentially different immunogenic profiles. In addition, our results show a greater proportion of F protein T cell epitope content conservation among recent epidemic strains, whereas the G protein T cell epitope content was decreased. Importantly, our results suggest that RSV-A and RSV-B have different patterns of epitope drift and replacement and that RSV-B vaccines may need more frequent updates. Our study provides a novel framework to study RSV T cell epitope evolution. Understanding the patterns of T cell epitope conservation and change may be valuable for vaccine design and assessment.
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spelling doaj.art-425eb1f32a3c495e9b17ae9d594b72c42023-08-26T05:31:14ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582023-01-01191e101036010.1371/journal.pcbi.1010360Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.Jiani ChenSwan TanVasanthi AvadhanulaLeonard MoisePedro A PiedraAnne S De GrootJustin BahlHuman respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally validated. We applied multidimensional scaling (MDS) to construct T cell epitope landscapes to investigate the diversity and evolution of T cell profiles across different RSV strains. We find the RSV strains are clustered into three RSV-A groups and two RSV-B groups on this T epitope landscape. These clusters represent divergent RSV strains with potentially different immunogenic profiles. In addition, our results show a greater proportion of F protein T cell epitope content conservation among recent epidemic strains, whereas the G protein T cell epitope content was decreased. Importantly, our results suggest that RSV-A and RSV-B have different patterns of epitope drift and replacement and that RSV-B vaccines may need more frequent updates. Our study provides a novel framework to study RSV T cell epitope evolution. Understanding the patterns of T cell epitope conservation and change may be valuable for vaccine design and assessment.https://doi.org/10.1371/journal.pcbi.1010360
spellingShingle Jiani Chen
Swan Tan
Vasanthi Avadhanula
Leonard Moise
Pedro A Piedra
Anne S De Groot
Justin Bahl
Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
PLoS Computational Biology
title Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
title_full Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
title_fullStr Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
title_full_unstemmed Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
title_short Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus.
title_sort diversity and evolution of computationally predicted t cell epitopes against human respiratory syncytial virus
url https://doi.org/10.1371/journal.pcbi.1010360
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