The application of a safe neutralization assay for Ebolavirus using
lentivirus-based pseudotyped virus
Abstract
Ebolavirus (EBOV) is responsible for several EBOV disease (EVD)
outbreaks in Africa, with a fatality rate of up to 90%. During
2014-2016, An epidemic of EVD spread throughout Sierra Leone, Guinea and
Liberia, and killed over 11,000 people. EBOV began to circulate again in
the Democratic Republic of Congo in 2018. Due to the need for a BSL-4
facility to manipulate this virus, the development and improvement of
specific therapeutics has been hindered. As a result, it is imperative
to perform reliable research on EBOV under lowered BSL restrictions. In
this study, we developed a safe neutralization assay based on
pseudotyped EBOV, which incorporates the glycoprotein of the 2014 EBOV
epidemic strain into a lentivirus vector. Our results demonstrated that
the tropism of pseudotyped EBOV was similar to that of authentic EBOV,
but with only one infection cycle. And neutralizing activity of both
authentic EBOV and pseudotyped EBOV were compared in neutralization
assay using three different samples of antibody-based reagents against
EBOV, similar results were obtained. In addition, an indirect ELISA was
performed to show the relationship between IgG and neutralizing antibody
against EBOV detected by our pseudotyped EBOV-based neutralization
assay. As expected, the neutralizing antibody titers varied with the IgG
titers detected by indirect ELISA, and a correlation between the results
of the two assays was identified. By comparison with two different
assays, the reliability of the results detected by the pseudotyped
EBOV-based neutralization assay was confirmed. Collectively, in the
absence of BSL-4 restrictions, pseudotyped EBOV production and
neutralizing activity evaluation can be performed safely and in a manner
that is neither labor- nor time-consuming, providing a simple and safe
method for EBOV-neutralizing antibody detection and the assessment of
immunogenicity of EBOV vaccines. All these remarkable advantages of the
newly established assay highlight its potential to further application
in assessment of immunogenicity of EBOV vaccine candidates.