Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters

Venkatraman Siddharthan; Jinxin Miao; Arnaud J Van Wettere; Rong Li; Hua Wu; Eddie Sullivan; Jinan Jiao; Jay W Hooper; David Safronetz; John D Morrey; Justin G Julander; Zhongde Wang

doi:10.3390/v11020092

Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters

Viruses. 2019 Jan 22;11(2):92. doi: 10.3390/v11020092.

Authors

Venkatraman Siddharthan^{1

2}, Jinxin Miao^{3

4}, Arnaud J Van Wettere⁵, Rong Li⁶, Hua Wu⁷, Eddie Sullivan⁸, Jinan Jiao⁹, Jay W Hooper¹⁰, David Safronetz¹¹, John D Morrey^{12

13}, Justin G Julander^{14

15}, Zhongde Wang¹⁶

Affiliations

¹ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
² Institute for Antiviral Research, and Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
³ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
⁴ Department of Pathology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450066, China. [email protected].
⁵ Utah Veterinary Diagnostics Laboratory, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
⁶ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
⁷ SAB Biotherapeutics, Sioux Falls, SD 57104, USA. [email protected].
⁸ SAB Biotherapeutics, Sioux Falls, SD 57104, USA. [email protected].
⁹ SAB Biotherapeutics, Sioux Falls, SD 57104, USA. [email protected].
¹⁰ Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. [email protected].
¹¹ Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E, Canada. [email protected].
¹² Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
¹³ Institute for Antiviral Research, and Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
¹⁴ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
¹⁵ Institute for Antiviral Research, and Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].
¹⁶ Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. [email protected].

Abstract

Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain⁻Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection.

Keywords: STAT2 KO hamster; Zika virus; testis; therapeutic; transchromosomal bovine antibody.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Antibodies, Neutralizing / immunology
Antibodies, Neutralizing / therapeutic use*
Antibodies, Viral / immunology
Antibodies, Viral / therapeutic use*
Cattle
Cricetinae
Disease Models, Animal
Female
Gene Knockout Techniques
Humans
Immunization, Passive*
Male
STAT2 Transcription Factor / genetics*
Testis / pathology
Testis / virology
Zika Virus
Zika Virus Infection / prevention & control*
Zika Virus Infection / therapy*

Substances

Antibodies, Neutralizing
Antibodies, Viral
STAT2 Transcription Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding