美国宾夕法尼亚大学佩雷尔曼医学院Pablo Tebas团队研究了抗寨卡病毒DNA疫苗的安全性和免疫原性。2021年9月15日出版的《新英格兰医学杂志》发表了这项成果。

虽然寨卡病毒（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-巴利综合征也有很好的描述。目前还没有针对寨卡病毒感染的批准疫苗。

在这项1期、开放标签的临床试验中，研究组评估了一种合成一致的DNA疫苗（GLS-5700）的安全性和免疫原性，该疫苗编码ZIKV前膜蛋白和包膜蛋白，随机招募两组参与者，每组20名。在基线检查、4周和12周时，参与者皮内注射1 mg或2 mg疫苗，每次注射后进行电穿孔（使用脉冲电场将DNA序列导入细胞）。

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%是西班牙裔。在14周（即第三次注射疫苗后）的中期分析中，未报告严重不良事件。大约50%的参与者在接种部位出现局部反应（例如注射部位疼痛、发红、肿胀和瘙痒）。第三次注射疫苗后，在所有受试者中检测到结合抗体（通过酶联免疫吸附试验测定），接种1 mg和2 mg疫苗的受试者的几何平均滴度分别为1642和2871。

在Vero细胞分析中，62%的样本产生中和抗体。在神经细胞分析中，70%的血清样本对ZIKV感染有90%的抑制，95%的样本对ZIKV感染有50%的抑制。112只IFNAR敲除小鼠（由编码干扰素-α和干扰素-β受体基因缺失的小鼠一起繁育）接受腹腔注射接种疫苗后的血清，其中103只（92%）免遭ZIKV-PR209毒株的致命攻击；而接受基线血清的小鼠无一存活。存活率与中和滴度无关。

研究结果表明，在1期的开放标签临床试验中，DNA疫苗引发抗ZIKV免疫反应。仍需进一步的研究来更好地评估疫苗的安全性和有效性。

附：英文原文

Title: Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine

Author: Pablo Tebas, M.D.,, Christine C. Roberts, Ph.D.,, Kar Muthumani, Ph.D.,, Emma L. Reuschel, Ph.D.,, Sagar B. Kudchodkar, Ph.D.,, Faraz I. Zaidi, M.S.,, Scott White, M.D.,, Amir S. Khan, Ph.D.,, Trina Racine, Ph.D.,, Hyeree Choi, B.S.,, Jean Boyer, Ph.D.,, Young K. Park, J.D.,, Sylvie Trottier, M.D.,, Celine Remigio, D.P.T., R.N.,, Diane Krieger, M.D.,, Susan E. Spruill, M.S.,, Mark Bagarazzi, M.D.,, Gary P. Kobinger, Ph.D.,, David B. Weiner, Ph.D.,, and Joel N. Maslow, M.D., Ph.D.

Issue&Volume: 2021-09-15

Abstract:

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.

DOI: 10.1056/NEJMoa1708120

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1708120