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Next-Generation Sequencing of Human Antibody Repertoires for Exploring B-cell Landscape, Antibody Discovery and Vaccine Development

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The advent of next-generation sequencing (NGS) technologies for the comprehensive analysis of human antibody repertoires has opened up a new way of looking at B-cell immune landscapes with unprecedented resolution. NGS enables large-scale B-cell receptor (BCR) repertoire profiling and the annotation of ...

The advent of next-generation sequencing (NGS) technologies for the comprehensive analysis of human antibody repertoires has opened up a new way of looking at B-cell immune landscapes with unprecedented resolution. NGS enables large-scale B-cell receptor (BCR) repertoire profiling and the annotation of molecular-level immunogenetic data including V/D/J gene usage, combinatorial rearrangement, junctional diversity, and somatic mutation—all of which reveal the complex mechanisms underlying B-cell diversification and adaptive immune responses. More recent advances in NGS technologies have led to the high-throughput sequencing of entire antibody variable heavy (VH) and light (VL) chains as well as natively paired VH:VL repertoires resulting in the identification of complete antibody clonotypes. Rapid progress in the development of immunoinformatics and computational analysis tools is helping to extract the most pertinent biological information from these high-dimensional datasets. Exploring B-cell receptor (BCR) repertoire clonal diversity with bioinformatics-aided NGS analysis has proven to have importance for the detection of clonal expansions in B-cell malignancies, the tracking of autoimmune BCRs, the discovery of functional antibodies without screening, and the enhanced understanding of antibody responses elicited by natural infection or vaccination and how these responses may be influenced by age. Among its major impacts, NGS of antibody repertoires from the HIV-1-infected individuals and mining their antibodyome have enabled the discovery of several broadly neutralizing antibodies (bnAbs). Further, the elucidation of maturation pathways of bnAbs in individuals could help for the B-cell lineage vaccine design. Moreover, the application of NGS to compare anti-viral antibody repertoires evoked by infection versus vaccination is expected to inform the development of improved vaccines which might optimally recapitulate the protective effects of infection such as influenza. NGS-based discovery of B-cell immunogenetics and molecular signatures specific to bnAbs could serve as surrogate markers to predict vaccine efficacy or even be counted as a metric for the universal influenza vaccines and others. Therefore, NGS of antibody repertoires holds great promise for breakthroughs in a variety of applications, but not limited to: immune biomarkers for infectious diseases or cancer, therapeutic antibody discovery, B-cell maturation pathway analysis for B-cell lineage vaccine development, and insights into how ageing influences the antibody repertoire.
Here, we focus on recent applications of NGS technologies to the analysis of human antibody repertoires. Accordingly, this Frontiers Research Topic will be devoted to timely publishing of original research, mini-reviews, hypotheses, future perspectives and commentaries from experts in the afore-mentioned research areas that will be useful for developing antibody-based diagnostics, therapeutics and challenging vaccines for improving human health.


Keywords: B-cell receptor repertoire, antibodies, immunoglobulin repertoire, VH:VL pairing, clonotypes, antibodyome, vaccination, next generation sequencing, bioinformatics, sequence analysis


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