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

PLoS Comput Biol. 2023 Jan 10;19(1):e1010360. doi: 10.1371/journal.pcbi.1010360. eCollection 2023 Jan.

Abstract

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.

MeSH terms

  • Antibodies, Viral
  • Epitopes, T-Lymphocyte
  • Humans
  • Respiratory Syncytial Virus Infections*
  • Respiratory Syncytial Virus, Human*
  • Viral Fusion Proteins / chemistry

Substances

  • Epitopes, T-Lymphocyte
  • Viral Fusion Proteins
  • Antibodies, Viral