Lancet：灭活寨卡病毒疫苗具有安全性以及免疫原性
最近三项临床I期试验结果分别表明，一种叫做ZPIV（Zika purified inactivated virus）的疫苗在受试者体内具有较高的安全性与免疫原型。该临床试验是由来自沃尔特里德陆军研究所（WRAIR）的科学家们领导完成的。WRAIR与来自HIH的研究者们共同完成的这项试验结果发表在最近一期的《Lancet》杂志上。“目前我们急需一种阻止寨卡病毒扩散的疫苗。众所周知，寨卡病毒能够导致新生儿缺陷以及发育障碍，同时也会对成年人以及儿童造成严重的健康影响”，开组NIAID的主任Anthony S. Fauci博士说道：“I期临床试验结果表明ZPIV疫苗具有安全性与有效性，具有阻止寨卡病毒传播的能力”。
http://cache1.bioon.com/webeditor/uploadfile/201712/20171207150541197.png
（感染非洲绿猴肾脏细胞的寨卡病毒（红色），图片来源：NIAID）
ZPIV疫苗候选物包含灭活的寨卡病毒颗粒，因此其不能够复制与传播。但由于其具有完整的病毒外壳，因此能够被机体免疫系统识别。
在参与I期临床试验的67名志愿者中，55名接种了上述疫苗，12名则接种了安慰剂。与疫苗共同接种的还包括一种包含铝盐的佐剂，能够帮助引发更强的免疫反应。所有参与者在四周之内接受了两次肌肉注射。
之后，研究者们检测了患者血液中的抗病毒抗体载量。结果显示，90%接种疫苗的患者在四周之内产生了针对性的抗体。
虽然研究者们还没有证明其抗体的产生水平能否达到保护机体不受感染的地步，但动物实验表明通过移植上述抗体进入小鼠体内能够有效抵抗小鼠感染寨卡病毒之后产生的病毒血症。
（生物谷 Bioon.com）
Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials
Martin R Gaudinski, MDa, †, Katherine V Houser, PhDa, †, Kaitlyn M Morabito, PhDa, Zonghui Hu, PhDb, Galina Yamshchikov, MSca, Ro Shauna Rothwell, PhDa, Nina Berkowitz, MPHa, Floreliz Mendoza, RNa, Jamie G Saunders, BSNa, Laura Novik, RNa, Cynthia S Hendel, CRNPa, LaSonji A Holman, FNPa, Ingelise J Gordon, RNa, Josephine H Cox, PhDa, Srilatha Edupuganti, MDd, Monica A McArthur, MDe, Nadine G Rouphael, MDd, Kirsten E Lyke, MDe, Ginny E Cummings, CRNPe, Sandra Sitar, MSca, Robert T Bailer, PhDa, Bryant M Foreman, MSc, Katherine Burgomaster, MSc, Rebecca S Pelc, PhDc, David N Gordon, MSc, Christina R DeMaso, MSc, Kimberly A Dowd, PhDc, Carolyn Laurencot, PhDa, Richard M Schwartz, PhDa, Sen NIH Investigator John R Mascola, MDa, Barney S Graham, MDa, Sen NIH Investigator Theodore C Pierson, PhDc, Julie E Ledgerwood, DOa, Grace L Chen, MDa, , , and the VRC 319 and VRC 320 study teams
Background
The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins.
Methods
We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18–35 years in VRC19 and 18–50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461.
Findings
VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 of 80 participants in VRC 319 and 36 of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 and 18 , respectively, in VRC 319 and 17 and 15 , respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials.
Interpretation
VRC5283 was well tolerated and has advanced to phase 2 efficacy testing.
http://www.sciencedirect.com/science/article/pii/S0140673617331057
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