Incomplete Recovery of Pneumococcal CD4 T Cell Immunity after Initiation of Antiretroviral Therapy in HIV-Infected Malawian Adults

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Sepako, Enoch ; Glennie, Sarah J. ; Jambo, Kondwani ; Mzinza, David ; Iwajomo, Oluwadamilola H. ; Banda, Dominic ; van Oosterhout, Joep J. ; A. Williams, Neil ; Gordon, Stephen ; Heyderman, Robert S. (2014)
  • Publisher: Public Library of Science
  • Journal: PLoS ONE, volume 9, issue 6 (eissn: 1932-6203)
  • Related identifiers: doi: 10.1371/journal.pone.0100640, pmc: PMC4069109
  • Subject: Microbial Pathogens | Research Article | Biology and Life Sciences | Microbiology | wc_503_5 | wc_217 | wc_503 | wc_503_2 | Immunity | Bacterial Pathogens | Immunodeficiency Viruses | Acquired Immune System | Medical Microbiology | Viral Pathogens | Streptococcus | qw_573 | Immune Response | Virology | qw_541 | Immune System | Immunology

HIV-infected African adults are at a considerably increased risk of life-threatening invasive pneumococcal disease (IPD) which persists despite antiretroviral therapy (ART). Defects in naturally acquired pneumococcal-specific T-cell immunity have been identified in HIV-infected adults. We have therefore determined the extent and nature of pneumococcal antigen-specific immune recovery following ART. HIV-infected adults were followed up at 3, 6 and 12 months after initiating ART. Nasopharyngeal swabs were cultured to determine carriage rates. Pneumococcal-specific CD4 T-cell immunity was assessed by IFN-γ ELISpot, proliferation assay, CD154 expression and intracellular cytokine assay. S. pneumoniae colonization was detected in 27% (13/48) of HIV-infected patients prior to ART. The rates remained elevated after 12 months ART, 41% (16/39) (p = 0.17) and significantly higher than in HIV-uninfected individuals (HIVneg 14%(4/29); p = 0.0147). CD4+ T-cell proliferative responses to pneumococcal antigens increased significantly to levels comparable with HIV-negative individuals at 12 months ART (p = 0.0799). However, recovery of the pneumococcal-specific CD154 expression was incomplete (p = 0.0015) as were IFN-γ ELISpot responses (p = 0.0040) and polyfunctional CD4+ T-cell responses (TNF-α, IL-2 and IFN-γ expression) (p = 0.0040) to a pneumolysin-deficient mutant strain. Impaired control of pneumococcal colonisation and incomplete restoration of pneumococcal-specific immunity may explain the persistently higher risk of IPD amongst HIV-infected adults on ART. Whether vaccination and prolonged ART can overcome this immunological defect and reduce the high levels of pneumococcal colonisation requires further evaluation.
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