Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle.
Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities.
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
John M
JM
Dye
SAB Biotherapeutics, Sioux Falls, South Dakota, United States of America.
Hua
H
Wu
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Jay W
JW
Hooper
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, Maryland, USA.
Surender
S
Khurana
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Ana I
AI
Kuehne
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, Maryland, USA.
Elizabeth M
EM
Coyle
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Ramon A
RA
Ortiz
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, Maryland, USA.
Sandra
S
Fuentes
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Andrew S
AS
Herbert
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, Maryland, USA.
Hana
H
Golding
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Russell A
RA
Bakken
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Jennifer M
JM
Brannan
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Steve A
SA
Kwilas
SAB Biotherapeutics, Sioux Falls, South Dakota, United States of America.
Eddie J
EJ
Sullivan
Viral and Rickettsial Diseases Department, Navy Medical Research Center, The Henry Jackson Foundation, Silver Spring, Maryland, USA.
Thomas C
TC
Luke
Novavax Inc, Gaithersburg, Maryland, USA.
Gale
G
Smith
Novavax Inc, Gaithersburg, Maryland, USA.
Gregory
G
Glenn
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University, Atlanta, Georgia, 30322, USA.
Wenfang
W
Li
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University, Atlanta, Georgia, 30322, USA.
Ling
L
Ye
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University, Atlanta, Georgia, 30322, USA.
Chinglai
C
Yang
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University, Atlanta, Georgia, 30322, USA.
Richard W
RW
Compans
The University of Georgia, Athens, Georgia, 30602, USA.
Ralph A
RA
Tripp
SAB Biotherapeutics, Sioux Falls, South Dakota, United States of America.
Jin-An
JA
Jiao
D000818:Animals; D030801:Animals, Genetically Modified; D000914:Antibodies, Viral / Q000097:blood* / Q000627:therapeutic use*; D002417:Cattle; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D020349:Surface Plasmon Resonance; D016896:Treatment Outcome
D000914:Antibodies, Viral; D007074:Immunoglobulin G