联合 13 价肺炎球菌结合疫苗和 23 价肺炎球菌多糖疫苗方案用于系统性红斑狼疮成人患者:肺炎球菌疫苗接种顺序是否影响免疫原性反应?巴西的一项单中心队列研究。

Combined 13-valent pneumococcal conjugate and 23-valent pneumococcal polysaccharide vaccine regimens for adults with systemic lupus erythematosus: Does the sequence of pneumococcal vaccination affect immunogenicity responses? A single-center cohort study in Brazil.

机构信息

Rheumatology Division, Department of Clinical Medicine, Universidade Federal Fluminense, Niterói, Brazil.

Department of Rheumatology, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Lupus. 2023 Apr;32(5):694-703. doi: 10.1177/09612033231153535. Epub 2023 Jan 27.

Abstract

OBJECTIVE

A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE.

METHODS

This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6 weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 μg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs.

RESULTS

Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination.

CONCLUSION

The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.

摘要

目的

目前建议系统性红斑狼疮(SLE)患者同时接种 13 价肺炎球菌结合疫苗(PCV13)和 23 价肺炎球菌多糖疫苗(PPSV23)。然而,关于该患者人群中序贯接种肺炎球菌疫苗所引起的免疫原性的数据却很少。在这项研究中,我们比较了 PCV13/PPSV23(间隔≥8 周)和 PPSV23/PCV13(间隔≥12 个月)两种接种策略在肺炎球菌疫苗初免的 SLE 成人中的短期抗体应答。

方法

这是一项在单中心队列中进行的纵向、开放性、准随机研究,纳入了 SLE 成人(18 岁或以上)。在两组接种疫苗后,在接种第一剂肺炎球菌疫苗前(时间点 T0)、初次接种后 4-6 周(T1)和加强接种后 4-6 周(T2)采集血样。我们主要关注 PCV13 和 PPSV23 之间的 12 个共有血清型,并在 T2 时比较两组的以下免疫原性结果:肺炎球菌抗体几何平均浓度(ApAb GMC)、ApAb 水平的升高倍数(FI-ApAb)、总血清保护率和总血清转化率。每个肺炎球菌血清型的保护水平设定为 1.3 μg/ml。我们使用多分析物免疫检测法来确定血清中 ApAbs 的水平。

结果

2019 年 4 月至 2020 年 1 月期间,共筛选了 34 例 SLE 患者,其中 16 例(平均年龄 39.4 岁,87.5%为女性,100%接受免疫抑制剂治疗)在 T2 时有可评估的免疫原性结果。PCV13/PPSV23 组(n=11 例)和 PPSV23/PCV13 组(n=5 例)之间接种肺炎球菌疫苗的中位时间间隔分别为 56 天和 16 个月。与 PPSV23 相比(PPSV23/PCV13 组),PCV13 (PCV13/PPSV23 组)作为初始疫苗接种产生了更好的 FI-ApAb、总血清转化率和总血清保护率,且在每一次接种肺炎球菌疫苗后 4-6 周均如此。在接受 PCV13/PPSV23 序贯接种的患者中,ApAb GMC 也呈现出增加的趋势。序贯接种肺炎球菌疫苗没有发现明显的安全性问题。

结论

在 SLE 成人中,PCV13 初免 PPSV23 加强的方案诱导了大多数免疫原性结果的抗体应答,优于 PPSV23/PCV13 方案。

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