A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge

Arban Domi,Heinz Feldmann,Patrick W Hanley,George K Lewis,Harriet L Robinson,Chiara Orlandi,Kyle Shifflett,Andrea Marzi,Nathanael Mccurley,Jackson Emanuel,Farshad Guirakhoo,Rahul Basu,Michael S Hellerstein,Friederike Feldmann,Robin Flinko

doi:10.1038/s41598-017-19041-y

Abstract

Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013–2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective immune responses. In this study, we report 100% protection against lethal EBOV infection in guinea pigs after prime/boost vaccination with MVA-EBOV. Furthermore, this MVA-EBOV protected macaques from lethal disease after a single dose or prime/boost vaccination. The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is the first report that a replication-deficient MVA vector can confer full protection against lethal EBOV challenge after a single dose vaccination in macaques.

Highlights

Are available, only studies have been published associating this vaccine approach with immunogenicity and only mild adverse effects[11,12]
This vector, designated MVA-EBOV, expresses GP and VP40 in vaccine-infected cells and vaccine capable of forming EBOV-like particles (VLPs) are released from these cells
Thin section electron microscopy documented the active budding of VLPs from these cells, and immuno-gold staining confirmed the display of EBOV GP on the surface of the VLPs (Fig. 1c,d)

Summary

Introduction

Are available, only studies have been published associating this vaccine approach with immunogenicity and only mild adverse effects[11,12] Another approach with promising pre-clinical efficacay data are virus-like particle-based vaccines (VLPs) consisting of the EBOV matrix protein VP40 and the glycoprotein (GP)[5]. This vaccine presents the antigens to the immune system in particles closely resembling authentic EBOV and elicits protective humoral and adaptive immune respones[5]. We analyzed the protective efficacy of this novel recombinant MVA-based EBOV vaccine in two well-established animal disease models for EBOV infection, the guinea pig and macaques

Methods

Results

Conclusion