基于埃博拉病毒样颗粒的疫苗可保护非人灵长类动物免受致命埃博拉病毒的攻击。

Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge.

作者信息

Warfield Kelly L, Swenson Dana L, Olinger Gene G, Kalina Warren V, Aman M Javad, Bavari Sina

机构信息

US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.

出版信息

J Infect Dis. 2007 Nov 15;196 Suppl 2:S430-7. doi: 10.1086/520583.

DOI:10.1086/520583

PMID:17940980

Abstract

BACKGROUND

Currently, there are no licensed vaccines or therapeutics for the prevention or treatment of infection by the highly lethal filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), in humans. We previously had demonstrated the protective efficacy of virus-like particle (VLP)-based vaccines against EBOV and MARV infection in rodents.

METHODS

To determine the efficacy of vaccination with Ebola VLPs (eVLPs) in nonhuman primates, we vaccinated cynomolgus macaques with eVLPs containing EBOV glycoprotein (GP), nucleoprotein (NP), and VP40 matrix protein and challenged the macaques with 1000 pfu of EBOV.

RESULTS

Serum samples from the eVLP-vaccinated nonhuman primates demonstrated EBOV-specific antibody titers, as measured by enzyme-linked immunosorbent assay, complement-mediated lysis assay, and antibody-dependent cell-mediated cytotoxicity assay. CD44+ T cells from eVLP-vaccinated macaques but not from a naive macaque responded with vigorous production of tumor necrosis factor- alpha after EBOV-peptide stimulation. All 5 eVLP-vaccinated monkeys survived challenge without clinical or laboratory signs of EBOV infection, whereas the control animal died of infection.

CONCLUSION

On the basis of safety and efficacy, eVLPs represent a promising filovirus vaccine for use in humans.

摘要

背景

目前，尚无经许可用于预防或治疗人类感染高致死性丝状病毒——埃博拉病毒（EBOV）和马尔堡病毒（MARV）的疫苗或治疗方法。我们之前已证明基于病毒样颗粒（VLP）的疫苗对啮齿动物的埃博拉病毒和马尔堡病毒感染具有保护效力。

方法

为确定用埃博拉病毒样颗粒（eVLP）对非人灵长类动物进行疫苗接种的效果，我们用含有埃博拉病毒糖蛋白（GP）、核蛋白（NP）和VP40基质蛋白的eVLP对食蟹猴进行疫苗接种，并用1000个噬斑形成单位（pfu）的埃博拉病毒对这些猴子进行攻击。

结果

通过酶联免疫吸附测定、补体介导的细胞溶解测定和抗体依赖性细胞介导的细胞毒性测定发现，来自接种eVLP的非人灵长类动物的血清样本显示出埃博拉病毒特异性抗体滴度。接种eVLP的食蟹猴的CD44 + T细胞在受到埃博拉病毒肽刺激后会大量产生肿瘤坏死因子-α，而未接种的食蟹猴的CD44 + T细胞则无此反应。所有5只接种eVLP的猴子在接受攻击后均存活，且没有埃博拉病毒感染的临床或实验室迹象，而对照动物死于感染。