Upregulation of IL-21 receptor on B cells and IL-21 secretion distinguishes novel 2009 H1N1 vaccine responders from nonresponders among HIV-infected persons on combination antiretroviral therapy

J Immunol. 2011 Jun 1;186(11):6173-81. doi: 10.4049/jimmunol.1100264. Epub 2011 Apr 29.


Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥ 1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R-expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunologic Memory / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / blood
  • Influenza, Human / complications
  • Influenza, Human / immunology
  • Interleukins / blood
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Prospective Studies
  • Receptors, Interleukin-21 / immunology*
  • Receptors, Interleukin-21 / metabolism
  • Time Factors
  • Up-Regulation
  • Young Adult


  • Anti-HIV Agents
  • Antibodies, Viral
  • Immunoglobulin G
  • Influenza Vaccines
  • Interleukins
  • Receptors, Interleukin-21
  • interleukin-21