Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
PLoS One. 2012;7(7):e42307. doi: 10.1371/journal.pone.0042307. Epub 2012 Jul 30.
Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count as follows: 20 ART-naïve (no prior ART), 62 ART-responders (received ART, and CD4 count >500 cells/µl), and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl). All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist) at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ)-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.
未经治疗的 HIV 感染会导致 B 细胞群体严重紊乱，并对疫苗接种反应低下。我们研究了治疗和未治疗的 HIV 患者中循环 B 细胞亚群与肺炎球菌结合疫苗抗体反应之间的关系。
95 名 HIV 感染成年人根据抗逆转录病毒治疗（ART）和 CD4+细胞计数分为以下三组：20 名未接受 ART 的患者（未接受过 ART，CD4 计数>500 个/μl）、62 名接受 ART 的患者（接受 ART，CD4 计数>500 个/μl）和 13 名免疫应答受损的患者（接受 ART 治疗超过 3 年，CD4 计数<500 个/μl）。所有受试者均在基线和三个月后两次接受双倍剂量 7 价肺炎球菌结合疫苗接种，同时接种或不接种 1mg CPG 7909（Toll 样受体 9 激动剂）。在接种疫苗前通过流式细胞术评估 B 细胞亚群。在基线和接种疫苗后 3、4 和 9 个月通过 ELISA 定量测定疫苗血清型 IgG 浓度。与免疫应答受损的患者相比，ART 应答者具有更多的同种型转换记忆 B 细胞和更多的边缘区（MZ）样 B 细胞。此外，与其他患者群体的 B 细胞相比，ART 初治患者具有更高浓度的过渡 B 细胞和浆母细胞。MZ 样、同种型转换记忆细胞和浆母细胞的浓度与接种疫苗后 3、4 和 9 个月的 IgG 浓度呈正相关。同种型转换记忆 B 细胞的浓度低是肺炎球菌结合疫苗反应不良的最强独立预测因子，这强调了 B 细胞亚群紊乱与 HIV 感染患者疫苗反应不良有关。
