title: DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome.
abstract: Polyclonal immunoglobulin-based medical products have been used successfully to treat diseases caused by viruses for more than a century. We demonstrate the use of DNA vaccine technology and transchromosomal bovines (TcBs) to produce fully human polyclonal immunoglobulins (IgG) with potent antiviral neutralizing activity. Specifically, two hantavirus DNA vaccines [Andes virus (ANDV) DNA vaccine and Sin Nombre virus (SNV) DNA vaccine] were used to produce a candidate immunoglobulin product for the prevention and treatment of hantavirus pulmonary syndrome (HPS). A needle-free jet injection device was used to vaccinate TcB, and high-titer neutralizing antibodies (titers >1000) against both viruses were produced within 1 month. Plasma collected at day 10 after the fourth vaccination was used to produce purified α-HPS TcB human IgG. Treatment with 20,000 neutralizing antibody units (NAU)/kg starting 5 days after challenge with ANDV protected seven of eight animals, whereas zero of eight animals treated with the same dose of normal TcB human IgG survived. Likewise, treatment with 20,000 NAU/kg starting 5 days after challenge with SNV protected immunocompromised hamsters from lethal HPS, protecting five of eight animals. Our findings that the α-HPS TcB human IgG is capable of protecting in animal models of lethal HPS when administered after exposure provides proof of concept that this approach can be used to develop candidate next-generation polyclonal immunoglobulin-based medical products without the need for human donors, despeciation protocols, or inactivated/attenuated vaccine antigen.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21709, USA. jay.w.hooper.civ@mail.mil.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Hooper
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21709, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Brocato
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21709, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kwilas
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21709, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hammerbeck
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21709, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Josleyn
authors.affiliation: Cedar Industries, Pierce, CO 80650, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Royals
authors.affiliation: Aldevron, LLC, Fargo, ND 58104, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ballantyne
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Jin-an
authors.initials: JA
authors.lastname: Jiao
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: SAB Biotherapeutics Inc., Sioux Falls, SD 57104, USA.
authors.forename: Eddie J
authors.initials: EJ
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D001682:Biological Availability; D002417:Cattle; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006476:Orthohantavirus / Q000276:immunology; D018804:Hantavirus Pulmonary Syndrome / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D029261:Sin Nombre virus / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D019444:Vaccines, DNA