title: Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Chief of No. 5 Biologicals Department, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kuming 650118, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Lumin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Warth
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kilby
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH 41006, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Bhargava
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'an men wai, Fengtai District, Beijing 100069, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 Xitoutiao, You'an men wai, Fengtai District, Beijing 100069, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilby
authors.affiliation: Chief of No. 5 Biologicals Department, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kuming 650118, China. Electronic address: liaogy@imbcams.com.cn.
authors.forename: Guoyang
authors.initials: G
authors.lastname: Liao
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: jianw@musc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D018988:Bacterial Translocation; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012329:RNA, Bacterial / Q000302:isolation & purification; D012336:RNA, Ribosomal, 16S / Q000302:isolation & purification
chemical_list: D044966:Anti-Retroviral Agents; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S
keywords: Antibody responses; B cells; HIV disease; Influenza vaccine