Mapping the Diversity and Evolution of RSV T Cell Epitopes for Vaccine Design

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory disease, particularly in infants, immunocompromised individuals, and older adults. The development of an RSV vaccine has been challenging, partly due to vaccine-enhanced disease caused by previous vaccine attempts, according to authors of a research article recently published in PLOS Computational Biology. However, recent advancements have paved the way for novel vaccine candidates and formulations.

Most current RSV vaccine designs focus on inducing a neutralizing immune response mediated by B cells. However, T cell immunity also plays a crucial role in clearing the virus, researchers said. Studies have shown that both CD4 and CD8 T cells contribute to protection against RSV, and a balanced cellular immune response is desired to promote virus clearance without causing immunopathology, the authors said.

RSV exhibits complex circulation patterns, with different genotypes cocirculating within the same community. This genetic diversity raises questions about the necessity of including multiple strains in an effective RSV vaccine. Researchers shared that while most current vaccine candidates are based on a laboratory strain, there is a risk of viral strains developing escape mutations. Researchers emphasized the importance of characterizing T cell epitope profiles across different strains for vaccine development.

The authors employed immunoinformatic approaches to predict T cell epitopes in RSV, focusing on the major surface proteins F and G. They evaluated lineage-specific T cell epitope profiles and created sequence-based T cell epitope landscapes to analyze the evolution of T cell immunity across different strains. 

Researchers identified conserved T cell epitopes in RSV, some of which have been experimentally validated. The results suggest that the F protein, despite being conserved, still undergoes epitope mutations across different lineages, while the G protein, known for its variability, exhibits potential conserved T cell epitopes. The analysis also revealed the correspondence between RSV T cell immunity clusters and their phylogenetic relationships.

The study further assessed the proportion of cross-conserved T cell epitope content between vaccine strains and circulating strains. Including T cell epitopes from different strains within the same antigenic group might be important for RSV vaccine development, according to the findings.

Although the study focused on T cell epitopes in the F and G proteins, other RSV proteins may also contribute to vaccine efficacy, researchers said. The authors called for experimental validation of T cell epitope predictions and emphasized the need to understand population-level epitope conservation to optimize vaccination strategies. 

Reference:
Chen J, Tan S, Avadhanula V, et al. Diversity and evolution of computationally predicted T cell epitopes against human respiratory syncytial virus. PLoS Comput Biol. 2023;19(1):e1010360. doi:10.1371/journal.pcbi.1010360