Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization

Nat Commun. 2015 Apr 10;6:6565. doi: 10.1038/ncomms7565.

Abstract

Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Neutralizing / immunology
  • B-Lymphocytes / immunology
  • Base Sequence
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology*
  • Lentivirus Infections / immunology
  • Lentivirus Infections / prevention & control
  • Lentiviruses, Primate / immunology
  • Longitudinal Studies
  • Macaca mulatta
  • Molecular Sequence Data
  • RNA, Messenger / metabolism*
  • RNA, Viral / analysis
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / immunology*
  • Viral Load
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Immunoglobulins
  • RNA, Messenger
  • RNA, Viral
  • env Gene Products, Human Immunodeficiency Virus

Associated data

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