Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

Vaccine. 2016 Apr 7;34(16):1945-55. doi: 10.1016/j.vaccine.2015.12.038. Epub 2015 Dec 22.

Abstract

Background: There is increasing recognition of the role of B cell dysfunction in HIV pathogenesis, but little is known about how these perturbations may influence responses to vaccinations.

Methods: Healthy controls (n=16) and antiretroviral therapy (ART)-treated aviremic HIV-infected subjects (n=26) receiving standard-of-care annual influenza vaccinations were enrolled in the present study. Total bacterial 16S rDNA levels were assessed by quantitative polymerase chain reactions in plasma. Serologic responses were characterized by ELISA, hemagglutination inhibition assay (HI), and microneutralization, and cell-mediated responses were assessed by ELISPOT (antigen-specific IgG+ antibody-secreting cells (ASCs)) and flow cytometry at pre-vaccination (D0), day 7-10 (D7) and day 14-21 (D14) post-vaccination.

Results: Decreased peripheral CD4+ T cell absolute counts and increased frequencies of cycling and apoptotic B cells were found at baseline in HIV-infected subjects relative to healthy controls. In healthy controls, post-vaccination neutralizing activities were related to the frequencies of vaccine-mediated apoptosis and cycling of B cells, but not to CD4+ T cell counts. In patients, both baseline and post-vaccination neutralizing activities were directly correlated with plasma level of bacterial 16S rDNA. However, overall vaccine responses including antibody titers and fold changes were comparable or greater in HIV-infected subjects relative to healthy controls.

Conclusion: B cell function correlates with measures of recall humoral immunity in response to seasonal influenza vaccination in healthy controls but not in ART-treated patients.

Keywords: Antibody responses; B cells; HIV disease; Influenza vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Apoptosis
  • B-Lymphocytes / immunology*
  • Bacterial Translocation
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Influenza A Virus, H1N1 Subtype
  • Influenza A Virus, H3N2 Subtype
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Neutralization Tests
  • RNA, Bacterial / isolation & purification
  • RNA, Ribosomal, 16S / isolation & purification

Substances

  • Anti-Retroviral Agents
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Influenza Vaccines
  • RNA, Bacterial
  • RNA, Ribosomal, 16S