Sepako Enoch, Glennie Sarah J, Jambo Kondwani C, Mzinza David, Iwajomo Oluwadamilola H, Banda Dominic, van Oosterhout Joep J, A Williams Neil, Gordon Stephen B, Heyderman Robert S
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
PLoS One. 2014 Jun 24;9(6):e100640. doi: 10.1371/journal.pone.0100640. eCollection 2014.
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.
感染HIV的非洲成年人患危及生命的侵袭性肺炎球菌疾病（IPD）的风险显著增加，尽管接受了抗逆转录病毒治疗（ART），这种风险仍然存在。在感染HIV的成年人中，已发现自然获得的肺炎球菌特异性T细胞免疫存在缺陷。因此，我们确定了ART后肺炎球菌抗原特异性免疫恢复的程度和性质。对感染HIV的成年人在开始ART后的3个月、6个月和12个月进行随访。培养鼻咽拭子以确定携带率。通过IFN-γ ELISpot、增殖试验、CD154表达和细胞内细胞因子试验评估肺炎球菌特异性CD4 T细胞免疫。在ART前，27%（13/48）的HIV感染患者检测到肺炎链球菌定植。ART 12个月后，该比率仍保持在较高水平，为41%（16/39）（p = 0.17），且显著高于未感染HIV的个体（HIV阴性者为14%（4/29）；p = 0.0147）。在ART 12个月时，对肺炎球菌抗原的CD4 + T细胞增殖反应显著增加，达到与HIV阴性个体相当的水平（p = 0.0799）。然而，肺炎球菌特异性CD154表达的恢复不完全（p = 0.0015），对缺乏肺炎溶血素的突变菌株的IFN-γ ELISpot反应（p = 0.0040）和多功能CD4 + T细胞反应（TNF-α、IL-2和IFN-γ表达）（p = 0.0040）也是如此。对肺炎球菌定植的控制受损以及肺炎球菌特异性免疫的不完全恢复，可能解释了接受ART的HIV感染成年人中IPD风险持续较高的原因。疫苗接种和延长ART能否克服这种免疫缺陷并降低肺炎球菌的高定植水平，需要进一步评估。
