Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Abstract

SummaryNumerous antibodies have been identified from HIV‐1‐infected donors that neutralize diverse strains of HIV‐1. These antibodies may provide the basis for a B cell‐mediated HIV‐1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics‐based approach to understand the genetic and immunologic processes controlling the development of HIV‐1‐neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next‐generation sequencing of B‐cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large‐scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information‐rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi‐dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution‐enhancing tools, which collectively embody an information‐driven discovery engine aimed toward the development of effective B cell‐based vaccines.

Human adaptive immune receptor repertoire analysis—Past, present, and future

“…Aligners such as IMGT/V‐QUEST or IgBLAST are popular choices for the alignment steps, although more sophisticated modeling approaches for defining junctional base calls and gene segment identities such as partis have been described recently and may provide more accurate results for some sequences . These topics are reviewed in more detail in the article by Matsen and colleagues in this Issue.…”

“…Because the Ig loci are rearranged and mutated on the DNA level, it is important that clone calling is performed on the nucleotide sequence rather than the amino acid sequence. Finally, similar inferences can be employed across responses from different individuals to define convergent Ig receptor signatures …”

Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response

“…Recently, next-generation sequencing (NGS)-based antibody repertoire analysis has been used to provide a systemic view of humoral responses to antigen stimuli [13] such as viral infections [19] and vaccination [17,20,21]. Understanding the mechanism and dynamics underlying antibody generation can facilitate vaccine design and improve the prognosis of infectious diseases [13,22]. In this report, we isolated E-binding mAbs from a ZIKV-infected patient and performed NGS analysis of the IgH mRNA repertoires to gain insight into the dynamics of the antibody response after infection.…”

The quest for an antibody‐based HIV vaccine

“…Understanding bnAb development and targeting naive B‐cell receptors by vaccine antigens has required the development of new computational biology methods and programs for inferring germline antibody sequences and constructing evolutionary trees of bnAbs. Kwong et al . outline their multiple ‘antibodyome’ approaches to computational analysis of the antibody response to HIV‐1.…”