Abstract
Ebola (EBOV), Marburg (MARV) and Sudan (SUDV) viruses are the three filoviruses which have caused the most fatalities in humans. Transmission from animals into the human population typically causes outbreaks of limited scale in endemic regions. In contrast, the 2013-16 outbreak in several West African countries claimed more than 11,000 lives revealing the true epidemic potential of filoviruses. This is further emphasized by the difficulty seen with controlling the 2018-2020 outbreak of EBOV in the Democratic Republic of Congo (DRC), despite the availability of two emergency use-approved vaccines and several experimental therapeutics targeting EBOV. Moreover, there are currently no vaccine options to protect against the other epidemic filoviruses. Protection of a monovalent EBOV vaccine against other filoviruses has never been demonstrated in primate challenge studies substantiating a significant void in capability should a MARV or SUDV outbreak of similar magnitude occur. Herein we show progress on developing vaccines based on recombinant filovirus glycoproteins (GP) from EBOV, MARV and SUDV produced using the Drosophila S2 platform. The highly purified recombinant subunit vaccines formulated with CoVaccine HT™ adjuvant have not caused any safety concerns (no adverse reactions or clinical chemistry abnormalities) in preclinical testing. Candidate formulations elicit potent immune responses in mice, guinea pigs and non-human primates (NHPs) and consistently produce high antigen-specific IgG titers. Three doses of an EBOV candidate vaccine elicit full protection against lethal EBOV infection in the cynomolgus challenge model while one of four animals infected after only two doses showed delayed onset of Ebola Virus Disease (EVD) and eventually succumbed to infection while the other three animals survived challenge. The monovalent MARV or SUDV vaccine candidates completely protected cynomolgus macaques from infection with lethal doses of MARV or SUDV. It was further demonstrated that combinations of MARV or SUDV with the EBOV vaccine can be formulated yielding bivalent vaccines retaining full efficacy. The recombinant subunit vaccine platform should therefore allow the development of a safe and efficacious multivalent vaccine candidate for protection against Ebola, Marburg and Sudan Virus Disease.
Highlights
The Filoviridae family of viruses includes several highly virulent pathogens, such as Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Marburg marburgvirus (MARV), which have caused sporadic and large-scale outbreaks in Central and West Africa
Vaccinated groups showed boosting of EBOV GP-specific IgG responses after the second and third doses of vaccine; antibody levels declined from week five to week eight in animals receiving two doses compared to sustained levels until viral challenge among animals receiving a third dose (p
Control animals succumbed to Ebola virus disease (EVD) by day 7 after viral challenge (Figure 1C)
Summary
The Filoviridae family of viruses includes several highly virulent pathogens, such as Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Marburg marburgvirus (MARV), which have caused sporadic and large-scale outbreaks in Central and West Africa. These viruses cause hemorrhagic fevers with case-fatality rates up to 90% [1, 2]. While virally vectored vaccines such as Ervebo have shown protective efficacy during experimental use in West Africa and DRC outbreaks [6], we expect that a recombinant subunit vaccine, especially a thermostabilized product [7], would pose less burdensome cold chain requirements for distribution and storage in endemic regions with poor infrastructure. Live virus vaccines are contraindicated for severely immunocompromised individuals and pregnant women [8] as viral replication of the vaccine strain may induce pathogenicity in vaccinees or in a developing fetus or neonate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
