Thomas Luke 1 , Richard S Bennett 2 , Dawn M Gerhardt 2 , Tracey Burdette 2 , Elena Postnikova 2 , Steven Mazur 2 , Anna N Honko 2 , Nicholas Oberlander 2 , Russell Byrum 2 , Dan Ragland 2 , Marisa St. Claire 2 , Krisztina B Janosko 2 , Gale Smith 3 , Gregory Glenn 3 , Jay Hooper 4 , John Dye 4 , Subhamoy Pal 1 , Kimberly A Bishop-Lilly 5 , Theron Hamilton 5 , Kenneth Frey 5 , Laura Bollinger 2 , Jiro Wada 2 , Hua Wu 6 , Jin-an Jiao 6 , Gene G Olinger 2 , Bronwyn Gunn 8 , Galit Alter 8 , Surender Khurana 9 , Lisa E Hensley 2 , Eddie Sullivan 6 , Peter B Jahrling 2 , 7
16 July 2018
Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.