@article{5c78dce5c10e42858dadafd7936d78b0,
title = "Recombinant Protein Filovirus Vaccines Protect Cynomolgus Macaques From Ebola, Sudan, and Marburg Viruses",
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{\texttrademark} 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.",
keywords = "Ebola virus, Marburg virus, Sudan virus, filovirus, non-human primates, preclinical efficacy studies, vaccine",
author = "Lehrer, {Axel T.} and Eleanore Chuang and Madhuri Namekar and Williams, {Caitlin A.} and Wong, {Teri Ann S.} and Lieberman, {Michael M.} and Alex Granados and John Misamore and Jake Yalley-Ogunro and Hanne Andersen and Geisbert, {Joan B.} and Agans, {Krystle N.} and Cross, {Robert W.} and Geisbert, {Thomas W.}",
note = "Funding Information: The described work was supported in part by grants R01AI119185 and R01AI132323 from NIH/NIAID, by grant P30GM103516 from the Centers of Biomedical Research Excellence, NIH/NIGMS and by institutional funding. NIH/NIAID grant number UC7AI094660 to UTMB supported BSL-4 operations of the Galveston National Laboratory. We further would like to acknowledge Hawaii Biotech, Inc. (Honolulu, HI) for providing the Drosphila S2 cell line for expression of SUDV GP, Mapp Biopharmaceutical (San Diego, CA) and Integrated Biotherapeutics (Rockville, MD) for the monoclonal antibodies used for antigen purification and Protherics Medicines Development (London, UK) for the gift of CoVaccine HT{\texttrademark} adjuvant. The authors would like to thank the UTMB Animal Resource Center for husbandry support of laboratory animals and Daniel Deer, Kevin Melody, and Chad Mire for assistance with the animal studies and Viktoriya Borisevich and Courtney Woolsey for assistance processing BSL-4 specimens. We further thank Eunjung Lim from the Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii for providing statistical analyses for these studies. Funding Information: The described work was supported in part by grants R01AI119185 and R01AI132323 from NIH/NIAID, by grant P30GM103516 from the Centers of Biomedical Research Excellence, NIH/NIGMS and by institutional funding. NIH/NIAID grant number UC7AI094660 to UTMB supported BSL-4 operations of the Galveston National Laboratory. We further would like to acknowledge Hawaii Biotech, Inc. (Honolulu, HI) for providing the Drosphila S2 cell line for expression of SUDV GP, Mapp Biopharmaceutical (San Diego, CA) and Integrated Biotherapeutics (Rockville, MD) for the monoclonal antibodies used for antigen purification and Protherics Medicines Development (London, UK) for the gift of CoVaccine HT{\texttrademark} adjuvant. The authors would like to thank the UTMB Animal Resource Center for husbandry support of laboratory animals and Daniel Deer, Kevin Melody, and Chad Mire for assistance with the animal studies and Viktoriya Borisevich and Courtney Woolsey for Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Lehrer, Chuang, Namekar, Williams, Wong, Lieberman, Granados, Misamore, Yalley-Ogunro, Andersen, Geisbert, Agans, Cross and Geisbert.",
year = "2021",
month = aug,
day = "18",
doi = "10.3389/fimmu.2021.703986",
language = "English (US)",
volume = "12",
journal = "Frontiers in immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}