Frontiers in Immunology (Sep 2018)

A Comprehensive Analysis of the T and B Lymphocytes Repertoire Shaped by HIV Vaccines

  • Longlong Wang,
  • Longlong Wang,
  • Longlong Wang,
  • Wei Zhang,
  • Wei Zhang,
  • Liya Lin,
  • Liya Lin,
  • Xiao Li,
  • Xiao Li,
  • Nitin K. Saksena,
  • Nitin K. Saksena,
  • Jinghua Wu,
  • Jinghua Wu,
  • Shiyu Wang,
  • Shiyu Wang,
  • Shiyu Wang,
  • Joseph G. Joyce,
  • Xiuqing Zhang,
  • Xiuqing Zhang,
  • Huanming Yang,
  • Huanming Yang,
  • Jian Wang,
  • Jian Wang,
  • I-Ming Wang,
  • Xiao Liu,
  • Xiao Liu

DOI
https://doi.org/10.3389/fimmu.2018.02194
Journal volume & issue
Vol. 9

Abstract

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The exploitation of various human immunodeficiency virus type-1 (HIV-1) vaccines has posed great challenges for the researchers in precisely evaluating the vaccine-induced immune responses, however, the understanding of vaccination response suffers from the lack of unbiased characterization of the immune landscape. The rapid development of high throughput sequencing (HTS) makes it possible to scrutinize the extremely complicated immunological responses during vaccination. In the current study, three vaccines, namely N36, N51, and 5-Helix based on the HIV-1 gp41 pre-hairpin fusion intermediate were applied in rhesus macaques. We assessed the longitudinal vaccine responses using HTS, which delineated the evolutionary features of both T cell and B cell receptor repertoires with extreme diversities. Upon vaccination, we unexpectedly found significant discrepancies in the landscapes of T-cell and B-cell repertoires, together with the detection of significant class switching and the lineage expansion of the B cell receptor or immunoglobulin heavy chain (IGH) repertoire. The vaccine-induced expansions of lineages were further evaluated for mutation rate, lineage abundance, and lineage size features in their IGH repertoires. Collectively, these findings conclude that the N51 vaccine displayed superior performance in inducing the class-switch of B cell isotypes and promoting mutations of IgM B cells. In addition, the systematic HTS analysis of the immune repertoires demonstrates its wide applicability in enhancing the understanding of immunologic changes during pathogen challenge, and will guide the development, evaluation, and exploitation of new generation of diagnostic markers, immunotherapies, and vaccine strategies.

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