Ebola Virus Glycoprotein Domains Associated with Protective Efficacy.

Bharti Bhatia,Wakako Furuyama,Thomas Hoenen,Heinz Feldmann,Andrea Marzi

doi:10.3390/vaccines9060630

Abstract

Ebola virus (EBOV) is the cause of sporadic outbreaks of human hemorrhagic disease in Africa, and the best-characterized virus in the filovirus family. The West African epidemic accelerated the clinical development of vaccines and therapeutics, leading to licensure of vaccines and antibody-based therapeutics for human use in recent years. The most widely used vaccine is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) (VSV-EBOV). Due to its favorable immune cell targeting, this vaccine has also been used as a base vector for the development of second generation VSV-based vaccines against Influenza, Nipah, and Zika viruses. However, in these situations, it may be beneficial if the immunogenicity against EBOV GP is minimized to induce a better protective immune response against the other foreign immunogen. Here, we analyzed if EBOV GP can be truncated to be less immunogenic, yet still able to drive replication of the vaccine vector. We found that the EBOV GP glycan cap and the mucin-like domain are both dispensable for VSV-EBOV replication. The glycan cap, however, appears critical for mediating a protective immune response against lethal EBOV challenge in mice.

Highlights

We have developed second-generation vaccine vectors based on VSVIn recent years, we have developed second-generation vaccine vectors based on vesicular stomatitis virus (VSV)-Ebola virus (EBOV)
The VSV-EBOV∆glycan cap (GC)∆MLD vector was generated by deleting aa 227–489 encoding the GC and MLD (∆GC∆MLD) (Figure 1A) in the EBOV GP and cloning this open reading frame into the VSV vector as previously described [18]
The presence of the EBOV GP∆GC∆MLD on VSV particles was analyzed by Western blot analysis from infected VeroE6 cell culture supernatants in comparison to previously rescued VSV wildtype (VSVwt), VSVEBOV [18] and VSV-EBOV∆MLD [17] (Figure 1B)

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Filoviruses were identified in 1967 and have become known to cause severe human disease with case fatality rates of up to 90% [1]. The family Filoviridae is divided into 6 genera and 11 species, and includes several human-pathogenic viruses [2]. Ebola virus (EBOV) and Marburg virus (MARV) are the best-known members of this virus family because infrequent spill-over events into the human population with subsequent humanto-human transmission cause outbreaks of MARV disease and EBOV disease (EVD) [3]

Methods

Results

Conclusion