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.

Polysaccharide-specific B cell responses to vaccination in humans

“…A shift in B cell populations has also been implicated in the increased susceptibility of HIV-infected children to pneumococcal disease. 42 Here, children with HIV were found to have reduced numbers of circulating mature, naïve and resting B MEM , with an over-representation of mature, activated B cells.…”

Immune reconstitution and vaccination outcome in HIV-1 infected children

“…36 Response to the PCV vaccine is mostly mediated by B-cells; in this respect, depletion of B-cell subsets and pneumococcus-specific memory B-cells has recently been reported in HIV-1 infected African children with invasive pneumococcal disease despite a proportion of CD4 + T-cells being over 15%. 98 Therefore, results from these studies suggest that evaluating immune responses to pneumococcal vaccination in HIV-1 VZV belongs to the family of herpes viruses, therefore formation of varicella specific CD8 + T-cells is particularly important to prevent reactivation and infection following vaccination. In view of this, positive responses to vaccination in HIV-1 infected children have also been evaluated by varicella-specific lymphoproliferative assay (LPA) with stimulation indices (SI) above 3.…”

“…In support of this, the number of publications reporting the set-up of new antigen-specific B-cell ELISpot is increasing in the literature. 36,98,122 Application of such methods may be beneficial for vaccine design not only for HIV-1 infected patients but also for patients with other primary and secondary immune diseases presenting with similar immune disorders.…”

Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection

“…These observations support the hypothesis that HIV infection impacts upon acquired immunity in such a way as to affect the immune response to some pneumococcal serotypes more than others. In healthy individuals, serotype-specific IgG responses to PCV vary according to serotype, despite uniform T-cell responses to vaccine carrier protein [26]. It has been suggested that this may be a result of variations in B-cell repertoire [26].…”

“…In healthy individuals, serotype-specific IgG responses to PCV vary according to serotype, despite uniform T-cell responses to vaccine carrier protein [26]. It has been suggested that this may be a result of variations in B-cell repertoire [26]. Reports from our own group and others have demonstrated alterations in B-cell phenotype in the context of HIV [27–36], which can be related to both naturally acquired and vaccine-induced pneumococcal immunity [27,32,34].…”