title: Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients.
abstract: BACKGROUND
  Mechanisms underlying the failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood.
  
  
  OBJECTIVE
  To investigate innate immune factors regulating B-cell function in HIV-infected persons and to correlate them with serologic responses to H1N1/09 vaccine.
  
  
  METHODS
  We evaluated immunologic characteristics of 17 HIV-infected patients and 8 healthy controls (HCs) at 0, 7, and 28 days (designated T0, T1, and T2) following a single 15-μg dose of nonadjuvanted H1N1/09 influenza vaccine by using flow cytometry, ELISpot, and ELISA. All HCs and 9 patients (53%) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2.
  
  
  RESULTS
  In vaccine responders and HCs, serum levels of BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody-secreting cells increased at T2 in vaccine responders and HCs in ex vivo H1N1 antigen-stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine nonresponder patients at T2. At T0, vaccine nonresponders had lower frequencies of BAFF receptor and TACI-expressing memory B cells than did responders.
  
  
  CONCLUSIONS
  Impaired memory B-cell responses, deficiencies in serum BAFF and APRIL, and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pallikkuth
authors.forename: Sudheesh Pilakka
authors.initials: SP
authors.lastname: Kanthikeel
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Silva
authors.forename: Margaret
authors.initials: M
authors.lastname: Fischl
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pahwa
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007252:Influenza Vaccines; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13