title: mAbs and Ad-vectored IFN-α therapy rescue Ebola-infected nonhuman primates when administered after the detection of viremia and symptoms.
abstract: ZMAb is a promising treatment against Ebola virus (EBOV) disease that has been shown to protect 50% (two of four) of nonhuman primates (NHPs) when administered 2 days post-infection (dpi). To extend the treatment window and improve protection, we combined ZMAb with adenovirus-vectored interferon-α (Ad-IFN) and evaluated efficacy in EBOV-infected NHPs. Seventy-five percent (three of four) and 100% (four of four) of cynomolgus and rhesus macaques survived, respectively, when treatment was initiated after detection of viremia at 3 dpi. Fifty percent (two of four) of the cynomolgus macaques survived when Ad-IFN was given at 1 dpi, followed by ZMAb starting at 4 dpi, after positive diagnosis. The treatment was able to suppress viremia reaching ~10(5) TCID50 (median tissue culture infectious dose) per milliliter, leading to survival and robust specific immune responses. This study describes conditions capable of saving 100% of EBOV-infected NHPs when initiated after the presence of detectable viremia along with symptoms.
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.forename: Lisa
authors.initials: L
authors.lastname: Fernando
authors.forename: Jonathan
authors.initials: J
authors.lastname: Audet
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.forename: Jim
authors.initials: J
authors.lastname: Strong
authors.forename: Judie B
authors.initials: JB
authors.lastname: Alimonti
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D029043:Ebolavirus / Q000502:physiology*; D005822:Genetic Vectors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008251:Macaca / Q000276:immunology / Q000821:virology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000378:metabolism; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D016898:Interferon-alpha; D014764:Viral Proteins