Abstract
There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Here, we used a cross-filovirus immunogen based on conserved regions of the filovirus nucleoprotein, matrix and polymerase to construct simian adenovirus- and poxvirus MVA-vectored vaccines, and in a proof-of-concept study demonstrated a protection of the BALB/c and C57BL/6J mice against high, lethal challenges with Ebola and Marburg viruses, two distant members of the family, by vaccine-elicited T cells in the absence of GP antibodies.
Highlights
The family Filoviridae includes 5 distinct viruses in the Ebolavirus genus: Zaire Ebola virus (EBOV), Sudan virus (SUDV), Reston virus (RESTV), Tai Forest virus (TAFV), and Bundibugyo virus (BDBV); 2 viruses in the Marburg-virus genus: Marburg virus (MARV) and Ravn virus (RAVV); and 1 virus in the Cuevavirus genus: Lloviu virus (LLOV)
We demonstrate the principle that cellular responses can protect two strains of mice against a high lethal virus challenge of 1000 LD50 in the absence of glycoprotein antibodies, but a single epigraph T–cell vaccine can do so against distant members of the filovirus family, EBOV and MARV
At least seven vaccine platforms vectored by human and simian adenoviruses HAdV-5, HAdV-26, ChAdV-3, vesicular stomatitis virus (VSV), human cytomegalovirus, modified vaccinia virus Ankara (MVA), plasmid DNA, subunit proteins and virus-like particles have been tested in nonhuman primates (NHPs) and encouraging results were obtained with two candidates, replicating VSV-ZEBOV (EBOV) and non-replicating ChAd3-ZEBOV, showing a single dose efficacy against EBOV challenge [3, 4]
Summary
The family Filoviridae includes 5 distinct viruses in the Ebolavirus genus: Zaire Ebola virus (EBOV), Sudan virus (SUDV), Reston virus (RESTV), Tai Forest virus (TAFV), and Bundibugyo virus (BDBV); 2 viruses in the Marburg-virus genus: Marburg virus (MARV) and Ravn virus (RAVV); and 1 virus in the Cuevavirus genus: Lloviu virus (LLOV). There have been over 50 recorded zoonotic outbreaks causing hemorrhagic fevers in humans and non-human primates with 90% fatality rates [1, 2]. At least seven vaccine platforms vectored by human and simian (chimpanzee) adenoviruses HAdV-5, HAdV-26, ChAdV-3, vesicular stomatitis virus (VSV), human cytomegalovirus, modified vaccinia virus Ankara (MVA), plasmid DNA, subunit proteins and virus-like particles have been tested in nonhuman primates (NHPs) and encouraging results were obtained with two candidates, replicating VSV-ZEBOV (EBOV) and non-replicating ChAd3-ZEBOV, showing a single dose efficacy against EBOV challenge [3, 4]. Before the 2013 epidemic, only one vaccine reached phase 1 trial in humans and was abandoned. Facing the 2013 epidemic, the most promising vaccines were moved to clinical trials [5,6,7,8,9,10] and one, rVSV-ZEBOV reported efficacy in a human phase 3 trial [6]. During the 2018 Ebola outbreak in the Democratic Republic of Congo, death toll was reduced to 29 due to a number of factors; the rVSV-ZEBOV vaccine was experimentally deployed, but no data indicated its contribution to the reduced outbreak
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