Deteriorating pneumococcal-specific B-cell memory in minimally symptomatic African children with HIV infection
Iwajomo, O.H.; Finn, A.; Moons, P.; Nkhata, R.; Sepako, E.; Ogunniyi, A.D.; Williams, N.A.; Heyderman, R.S.
Journal of Infectious Diseases 204(4): 534-543
2011
ISSN/ISBN: 1537-6613 PMID: 21791655 DOI: 10.1093/infdis/jir316Document Number: 225952
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.