title: Deteriorating pneumococcal-specific B-cell memory in minimally symptomatic African children with HIV infection.
abstract: Invasive pneumococcal disease is a leading cause of human immunodeficiency virus (HIV)-associated mortality in sub-Saharan African children. Defective T-cell-mediated immunity partially explains this high disease burden, but there is an increased risk of invasive pneumococcal disease even in the context of a relatively preserved percentage of CD4 cells. We hypothesized that impaired B-cell immunity to this pathogen further amplifies the immune defect. We report a shift in the B-cell compartment toward an apoptosis-prone phenotype evident early in HIV disease progression. We show that, although healthy HIV-uninfected and minimally symptomatic HIV-infected children have similar numbers of isotype-switched memory B cells, numbers of pneumococcal protein antigen-specific memory B cells were lower in HIV-infected than in HIV-uninfected children. Our data implicate defective naturally acquired B-cell pneumococcal immunity in invasive pneumococcal disease causation in HIV-infected children and highlight the need to study the functionality and duration of immune memory to novel pneumococcal protein vaccine candidates in order to optimize their effectiveness in this population.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, United Kingdom. damilola.iwajomo@gmail.com
authors.forename: Oluwadamilola H
authors.initials: OH
authors.lastname: Iwajomo
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.forename: Peter
authors.initials: P
authors.lastname: Moons
authors.forename: Rose
authors.initials: R
authors.lastname: Nkhata
authors.forename: Enoch
authors.initials: E
authors.lastname: Sepako
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002353:Carrier State; D002648:Child; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007156:Immunologic Memory / Q000502:physiology*; D007223:Infant; D008295:Malawi / Q000453:epidemiology; D008297:Male; D011008:Pneumococcal Infections / Q000209:etiology / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D023201:CD40 Ligand