School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Front Immunol. 2024 Apr 3;15:1298471. doi: 10.3389/fimmu.2024.1298471. eCollection 2024.
In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine.
A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD.
Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis.
Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.
鉴于 COVID-19 大流行对公众健康造成的负担，提高 COVID-19 疫苗的安全性和免疫原性备受关注。许多中药（TCM）制剂已被证明可有益地调节免疫。基于在小鼠中的初步实验表明，接种重组 SARS-CoV-2 S-RBD 蛋白后，补充藿香苏苓双花汤（HSSD）可显著提高血清抗 RBD IgG 滴度，我们进行了这项随机、双盲、安慰剂对照的临床试验，旨在评估口服 HSSD 在第三次同源接种科兴公司灭活的 COVID-19 疫苗（CVS）后对血清抗 RBD IgG 滴度的潜在免疫增强作用。
共 70 名参与者按 1:1 比例随机分配，接受第三剂 CVS 疫苗接种，并分别口服安慰剂或 HSSD 连续 7 天。通过记录局部和全身不良事件以及血液和尿液生化及肝肾功能检查来评估安全性。主要观察指标包括血清抗 RBD IgG 滴度、T 淋巴细胞亚群、血清 IgG 和 IgM 水平、补体成分（C3 和 C4）和血清细胞因子（IL-6 和 IFN-γ）。此外，还使用代谢组学技术分析了补充 HSSD 后的差异代谢物表达。
与安慰剂组相比，在接受第三次 CVS 疫苗接种后，HSSD 组的血清抗 RBD IgG 滴度显著升高，血清 IL-6 水平降低，血清 IgG、IgM、C3 和 C4 水平升高，细胞免疫得到改善，表现在淋巴细胞亚群分布的平衡偏差减少。两组均未记录到严重不良事件。血清代谢组学结果表明，HSSD 增强 CVS 疫苗免疫原性的机制与嘌呤代谢、维生素 B6 代谢、叶酸生物合成、精氨酸和脯氨酸代谢以及甾体激素生物合成的差异调节有关。
口服 HSSD 可增强年轻和成年个体对 CVS 疫苗的免疫原性。这项试验为评估中药免疫调节剂以提高对 COVID-19 疫苗的免疫反应提供了临床参考。
