Yang Haijing, Zhou Yang, Cheng Xin, Qiu Chao, Wang Shuo, Xia Yu, Huai Xuefen, Xiu Zhenning, Wang Jiarong, He Yue, Cao Guoying, Wei Qiong, Wang Jingjing, Ai Jingwen, Zhang Haochen, Zhang Yi, Zhang Jing, Zhang Wenhong, Wang Bin
Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200400, China.
Department of Infectious Disease, Huashan Hospital Affiliated to Fudan University, Shanghai 200400, China.
Vaccines (Basel). 2025 May 27;13(6):573. doi: 10.3390/vaccines13060573.
: pGX9501 is a prophylactic DNA vaccine encoding the spike protein of SARS-CoV-2 and can induce immune response in the human body so as to prevent COVID-19. With respect to non-clinical studies, pGX9501 has been demonstrated to induce both cellular and humoral immune responses in various animal models. It was found that the level of antibody titers following a two-dose regimen was higher than that following a single-dose regimen in nonhuman primate challenge model. : In China, a phase I, randomized, double-blind, placebo-controlled clinical trial has been conducted in Huashan Hospital, Shanghai, China to evaluate the safety, tolerability, and immunogenicity of DNA vaccine pGX9501 administered intradermally (ID) followed by electroporation (EP) in 45 Chinese healthy volunteers aged 18 to 59 years old. : No adverse events of special interest (AESIs), death, or treatment-related SAEs occurred in this study. All the treatment-related (vaccine or EP) adverse events (TRAEs) were of grade 1 and 2 in severity. The solicited AEs were reported in thirty-two (32/36, 88.9%) and nine (9/9, 100.0%) subjects, respectively, in the DNA vaccine and placebo group. The frequency of solicited AEs did not increase with vaccine dose level and frequency. The DNA vaccine pGX9501 effectively enhanced both humoral and cellular immune responses in a dose-dependent manner, with increased antibody GMTs and peak seroconversion rates observed on day 42. The significant rise in IFN-γ levels confirmed the vaccine's ability to induce cellular immune responses. Variations in the microbiome structure suggested a tangible impact of the gut microbiota on vaccine immunogenicity. : The findings from this study confirm the immunogenicity and safety of the DNA vaccine pGX9501 and point to the potential role of the gut microbiota in vaccine immune responses. These insights provide practical references for the future design and development of DNA vaccines.
pGX9501是一种预防性DNA疫苗，编码严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突蛋白，可在人体中诱导免疫反应，从而预防新型冠状病毒肺炎（COVID-19）。在非临床研究中，pGX9501已被证明能在各种动物模型中诱导细胞免疫和体液免疫反应。发现在非人灵长类动物攻毒模型中，两剂接种方案后的抗体滴度水平高于单剂接种方案。在中国，已在中国上海华山医院对45名年龄在18至59岁的中国健康志愿者进行了一项I期随机双盲安慰剂对照临床试验，以评估皮内注射（ID）后进行电穿孔（EP）接种DNA疫苗pGX9501的安全性、耐受性和免疫原性。本研究中未发生特别关注的不良事件（AESIs）、死亡或与治疗相关的严重不良事件（SAEs）。所有与治疗相关的（疫苗或EP）不良事件（TRAEs）严重程度均为1级和2级。在DNA疫苗组和安慰剂组中，分别有32名（32/36，88.9%）和9名（9/9，100.0%）受试者报告了预期不良事件（solicited AEs）。预期不良事件的发生率并未随疫苗剂量水平和接种次数增加。DNA疫苗pGX9501以剂量依赖的方式有效增强了体液免疫和细胞免疫反应，在第42天观察到抗体几何平均滴度（GMTs）增加和血清阳转率峰值。干扰素-γ水平的显著升高证实了该疫苗诱导细胞免疫反应的能力。微生物组结构的变化表明肠道微生物群对疫苗免疫原性有切实影响。本研究结果证实了DNA疫苗pGX9501的免疫原性和安全性，并指出了肠道微生物群在疫苗免疫反应中的潜在作用。这些见解为DNA疫苗的未来设计和开发提供了实际参考。
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