title: Inflammatory Markers and Immune Response to Pneumococcal Vaccination in HIV-Positive and -Negative Adults.
abstract: BACKGROUND
  Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated.
  
  
  OBJECTIVE
  To investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization.
  
  
  METHODS
  Markers of inflammation, C-reactive protein (CRP), IL-6, sCD27 and sCD30, were assessed in HIV-positive and -negative individuals as potential predictors of PPV23 response. Serum levels of B cell activating factor (BAFF), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B cell maturation antigen (BCMA) and B cell expression of BAFF-R, TACI, BCMA, CD40 and CD21 were assessed in total (unselected) and PPS23F (antigen)-specific B cells of PPV23 immunized HIV-positive and -negative individuals.
  
  
  RESULTS
  CRP, sCD27, sCD30 and BAFF were significantly elevated in the serum of HIV-positive individuals but did not adversely affect PPV23 response. Assessment of PPS-specific B cells revealed enhanced TACI and reduced BAFF-R expression compared to unselected B cells in HIV-positive and -negative individuals. Surface TACI was similar but soluble TACI was significantly lower in HIV-positive compared to HIV-negative individuals.
  
  
  CONCLUSIONS
  Current studies highlight a potential role for TACI in PPV23 response based on its enhanced expression on PPS-specific B cells. Although surface levels of TACI were similar, diminished soluble TACI (sTACI) in HIV-positive compared to HIV-negative individuals could potentially decrease BAFF responsiveness and Ig response. A better understanding of the role of TNF receptors could contribute to the design of improved pneumococcal vaccines.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02515240.
authors.affiliation: Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Iyer
authors.affiliation: Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: Noor M
authors.initials: NM
authors.lastname: Khaskhely
authors.affiliation: Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Leggat
authors.affiliation: Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Ohtola
authors.affiliation: Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Saul-McBeth
authors.affiliation: Department of Public Health, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America.
authors.forename: Sadik A
authors.initials: SA
authors.lastname: Khuder
authors.affiliation: Department of Medicine; Department of Infectious Diseases and Department of Microbiology and Immunology, 135 Rutledge Avenue, Charleston, South Carolina 29425, United States of America.
authors.forename: M A Julie
authors.initials: MA
authors.lastname: Westerink
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000276:immunology*; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D022242:Pneumococcal Vaccines; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein