抗寨卡病毒 DNA 疫苗的安全性和免疫原性。
Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.
机构信息
From the Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania (P.T.), and Wistar Institute (K.M., E.L.R., S.B.K., F.I.Z., H.C., D.B.W.), Philadelphia, and Inovio Pharmaceuticals, Plymouth Meeting (S.W., A.S.K., J.B., M.B.) - all in Pennsylvania; GeneOne Life Science, Seoul, South Korea (C.C.R., Y.K.P., C.R., S.E.S., J.N.M.); Infectious Diseases Research Centre-Université Laval, Quebec, QC, Canada (T.R., S.T., G.P.K.); QPS-Miami Research Associates, Miami, (D.K.); and the Department of Medicine, Morristown Medical Center, Morristown, NJ (J.N.M.).
出版信息
N Engl J Med. 2021 Sep 16;385(12):e35. doi: 10.1056/NEJMoa1708120.
BACKGROUND
Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection.
METHODS
In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks.
RESULTS
The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer.
CONCLUSIONS
In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).
背景
虽然 Zika 病毒（ZIKV）感染通常是自限性的，但其他相关并发症，如先天性出生缺陷和格林-巴利综合征，已有明确的描述。目前尚无针对 ZIKV 感染的批准疫苗。
方法
在这项 1 期、开放性临床试验中，我们评估了编码 ZIKV 膜前和包膜蛋白的合成、共识 DNA 疫苗（GLS-5700）在两组各 20 名参与者中的安全性和免疫原性。参与者接受 1mg 或 2mg 的疫苗皮内注射，每次注射后均在基线、4 周和 12 周时进行电穿孔（使用脉冲电场将 DNA 序列导入细胞）。
结果
参与者的中位年龄为 38 岁，60%为女性；78%为白人，22%为黑人；此外，30%为西班牙裔。在 14 周的中期分析（即第三次疫苗接种后），未报告严重不良事件。接种部位的局部反应（如注射部位疼痛、发红、肿胀和瘙痒）发生在约 50%的参与者中。在第三次疫苗接种后，所有参与者均检测到结合抗体（通过酶联免疫吸附试验测量），接受 1mg 和 2mg 疫苗的参与者的几何平均滴度分别为 1642 和 2871。在 Vero 细胞测定中，62%的样本中出现中和抗体。在神经元细胞测定中，70%的血清样本中有 90%抑制 ZIKV 感染，95%的样本中有 50%抑制。接种疫苗后的血清腹腔内注射可保护 112 只 IFNAR 敲除小鼠（通过缺失编码干扰素-α和干扰素-β受体的基因而繁殖）免受致命剂量 ZIKV-PR209 株的攻击（接受对照血清的小鼠无一存活）。生存与中和滴度无关。
结论
在这项 1 期、开放性临床试验中，DNA 疫苗引发了抗 ZIKV 的免疫反应。需要进一步研究以更好地评估疫苗的安全性和有效性。（由 GeneOne Life Science 等资助；ZIKA-001 ClinicalTrials.gov 编号，NCT02809443。）
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