The Adaptive Immune System—Repertoire Convergence and Its Impact on Vaccine Research
Vaccines play an important role in global public health, enabling our adaptive immune system to quickly recognize and fight against infectious disease. Successful vaccine development and improved efficacy requires researchers to understand the evolution of the adaptive immune response to disease-causing agents like SARS-CoV-2. Rapid vaccine development to address the crisis is a leading topic in the scientific community and studying repertoire convergence may help improve vaccine efficacy.
The adaptive immune system creates an immunological memory in response to infection, leading to an enhanced response for subsequent infections. The power of the adaptive immune system is due to the diverse genetic population of the T cells and B cells that make up the immune repertoire. The genetic diversity is driven by genetic rearrangements, as well as somatic hypermutations (SHMs) in B cells to potentially increase antibody affinity to an antigen. Vaccine development is based on the principals of adaptive immunity with a diverse repertoire, priming the immune system to fight disease faster and more effectively.
However, in a recent review paper it was noted there are instances where the immune repertoire may lack diversity. The army of T cells and B cells with different genetic sequences may result in the same amino acid sequence due to codon degeneracy and thus the same antigen recognition. This feature of the immune repertoire is called convergence and its understanding may help improve vaccine efficacy. By studying convergence, one can identify the “holes” in repertoire diversity, where B cells and T cells may not bind to a given antigen and therefore, a vaccine would not be effective. Chronic antigen stimulation may result in repertoire convergence, highlighting the potential to measure immunogenicity and the possibility of optimizing vaccine strategies.
Studying convergence and obtaining a deeper understanding of immune response requires a high throughput sequencing solution that can accurately quantify the different genetic arrangements and single nucleotide variants within the immune repertoire. The low substitution error rate of Ion Torrent™ targeted next-generation sequencing (NGS) technology combined with targeted immune repertoire assays enables sensitive measurements of convergence, which may be masked in other sequencing approaches. The simple end-to-end workflow with a comprehensive suite of analysis and visualization tools makes it easy for vaccine researchers to understand immune response to potentially improve vaccines.
The global impact of the SARS-CoV-2 crisis has highlighted the importance of vaccine development to combat infectious diseases. While there is more work to be done, choosing the right NGS solution to quantify challenging features of the repertoire, like convergence, will be key for vaccine researchers for current work and in the future.
Read the paper in Frontiers in Immunology.
 Fink K (2019) Can We Improve Vaccine Efficacy by Targeting T and B Cell Repertoire Convergence? Front. Immunol. 10:110. doi: 10.3389/fimmu.2019.00110
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