title: The impact of B-cell perturbations on pneumococcal conjugate vaccine response in HIV-infected adults.
abstract: Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count as follows: 20 ART-naïve (no prior ART), 62 ART-responders (received ART, and CD4 count >500 cells/µl), and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl). All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist) at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ)-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark. tgjohannesson@gmail.com
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Johannesson
authors.forename: Ole S
authors.initials: OS
authors.lastname: Søgaard
authors.forename: Martin
authors.initials: M
authors.lastname: Tolstrup
authors.forename: Mikkel S
authors.initials: MS
authors.lastname: Petersen
authors.forename: Jens M
authors.initials: JM
authors.lastname: Bernth-Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaard
authors.forename: Christian
authors.initials: C
authors.lastname: Erikstrup
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines