Protection of Nonhuman Primates against Two Species of Ebola Virus Infection with a Single Complex Adenovirus Vector

Abstract

Ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. To meet the need for a vaccine against the several types of Ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (EBO7) that expresses the glycoproteins of Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV) in a single complex adenovirus-based vector (CAdVax). We evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes of lethal challenge. EBO7 vaccine provided protection against both Ebola viruses by either route of infection. Significantly, protection against SEBOV given as an aerosol challenge, which has not previously been shown, could be achieved with a boosting vaccination. These results demonstrate the feasibility of creating a robust, multivalent Ebola virus vaccine that would be effective in the event of a natural virus outbreak or biological threat.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

“…Thus, our studies provide no evidence that an EBOV GP immunogen lacking NGSs on GP1 elicits novel protective immune responses to highly conserved regions of GP on the surfaces of extracellular SUDV particles. To date, the most effective broad-spectrum protection has been achieved through combinatorial vaccines that present proteins from multiple viral species to the host (11,39,44,(65)(66)(67). Taking this together with our results, a mixture of VSVΔG pseudotyped with representative GPs from the filovirus family could provide an efficient, tractable, and safe vaccine that warrants further investigation in other animal model systems.…”

“…A number of different vaccine platforms that express the filovirus glycoprotein (GP) have proven to be effective at protecting against lethal homotypic filovirus challenge in animal models (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Those platforms that have proved efficacious in at least one animal model include DNA plasmids, adenoviral vectors, virus-like particles, recombinant Venezuelan equine encephalitis virus particles, and infectious recombinant viruses, such as human parainfluenza virus type 3, rabies virus, cytomegalovirus, and vesicular stomatitis virus (VSV).…”

Development and Characterization of a Guinea Pig-Adapted Sudan Virus

“…Although multiple vaccines have been tested, including VSV (17,18), complex adenovirus (CAdVax) (19), Venezuelan equine encephalitis virus (VEEV) (20), and virus-like particles (VLPs) (21), candidate drugs have not yet been tested against SUDV infections in NHPs. One factor that can hinder these studies is the high cost of producing and testing compounds in large animals; it is simply not financially feasible to screen potential candidates in NHPs.…”

A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge

“…One platform, recombinant vesicular stomatitis virus, has demonstrated prophylactic and postexposure protection in nonhuman primates. Many of these candidates have shown outstanding technical utility-especially the viral vectors (11)(12)(13). However, although highly active in controlled clinical settings, these candidate vaccines pose challenges for incorporation into a national biodefense stockpile, in which longterm vaccine stability with minimal cold chain requirements for storage and distribution are key factors in a successful program.…”