Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination

Sci Rep. 2016 Nov 16:6:37229. doi: 10.1038/srep37229.

Abstract

Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Double-Blind Method
  • Drug Combinations
  • Humans
  • Immunization Schedule
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Influenza, Human / blood
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Polysorbates / administration & dosage
  • Squalene / administration & dosage
  • Vaccination / methods*
  • alpha-Tocopherol / administration & dosage

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Drug Combinations
  • Influenza Vaccines
  • Polysorbates
  • Squalene
  • AS03 adjuvant
  • alpha-Tocopherol