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

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2019 Jan 26

PMID 30678320

Citations 5

Authors

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

Affiliations

Soon will be listed here.

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 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.

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References

Calvet G, Aguiar R, Melo A, Sampaio S, de Filippis I, Fabri A . Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis. 2016; 16(6):653-660. DOI: 10.1016/S1473-3099(16)00095-5. View

Valderrama A, Diaz Y, Lopez-Verges S . Interaction of Flavivirus with their mosquito vectors and their impact on the human health in the Americas. Biochem Biophys Res Commun. 2017; 492(4):541-547. DOI: 10.1016/j.bbrc.2017.05.050. View

Wang Q, Yang H, Liu X, Dai L, Ma T, Qi J . Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus. Sci Transl Med. 2016; 8(369):369ra179. DOI: 10.1126/scitranslmed.aai8336. View

Deng Y, Zhang N, Li C, Tian M, Hao J, Xie X . Adenosine Analog NITD008 Is a Potent Inhibitor of Zika Virus. Open Forum Infect Dis. 2016; 3(4):ofw175. PMC: 5063548. DOI: 10.1093/ofid/ofw175. View

Sano A, Matsushita H, Wu H, Jiao J, Kasinathan P, Sullivan E . Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle. PLoS One. 2013; 8(10):e78119. PMC: 3813428. DOI: 10.1371/journal.pone.0078119. View

Julander J, Siddharthan V, Evans J, Taylor R, Tolbert K, Apuli C . Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model. Antiviral Res. 2016; 137:14-22. PMC: 5215849. DOI: 10.1016/j.antiviral.2016.11.003. View

Bounds C, Kwilas S, Kuehne A, Brannan J, Bakken R, Dye J . Human Polyclonal Antibodies Produced through DNA Vaccination of Transchromosomal Cattle Provide Mice with Post-Exposure Protection against Lethal Zaire and Sudan Ebolaviruses. PLoS One. 2015; 10(9):e0137786. PMC: 4589376. DOI: 10.1371/journal.pone.0137786. View

Sapparapu G, Fernandez E, Kose N, Cao B, Fox J, Bombardi R . Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice. Nature. 2016; 540(7633):443-447. PMC: 5583716. DOI: 10.1038/nature20564. View

Brasil P, Pereira Jr J, Moreira M, Ribeiro Nogueira R, Damasceno L, Wakimoto M . Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016; 375(24):2321-2334. PMC: 5323261. DOI: 10.1056/NEJMoa1602412. View

10.

Tripathi S, Balasubramaniam V, Brown J, Mena I, Grant A, Bardina S . A novel Zika virus mouse model reveals strain specific differences in virus pathogenesis and host inflammatory immune responses. PLoS Pathog. 2017; 13(3):e1006258. PMC: 5373643. DOI: 10.1371/journal.ppat.1006258. View

11.

Silver J, Ashbaugh C, Miles J, Wu H, Marecki G, Hwang J . Deployment of Transchromosomal Bovine for Personalized Antimicrobial Therapy. Clin Infect Dis. 2017; 66(7):1116-1119. DOI: 10.1093/cid/cix977. View

12.

Magnani D, Rogers T, Beutler N, Ricciardi M, Bailey V, Gonzalez-Nieto L . Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques. Sci Transl Med. 2017; 9(410). PMC: 6155977. DOI: 10.1126/scitranslmed.aan8184. View

13.

Siddharthan V, Van Wettere A, Li R, Miao J, Wang Z, Morrey J . Zika virus infection of adult and fetal STAT2 knock-out hamsters. Virology. 2017; 507:89-95. DOI: 10.1016/j.virol.2017.04.013. View

14.

Stein D, Golden J, Griffin B, Warner B, Ranadheera C, Scharikow L . Human polyclonal antibodies produced in transchromosomal cattle prevent lethal Zika virus infection and testicular atrophy in mice. Antiviral Res. 2017; 146:164-173. DOI: 10.1016/j.antiviral.2017.09.005. View

15.

Beigel J, Voell J, Kumar P, Raviprakash K, Wu H, Jiao J . Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study. Lancet Infect Dis. 2018; 18(4):410-418. PMC: 5871563. DOI: 10.1016/S1473-3099(18)30002-1. View

16.

Luke T, Wu H, Zhao J, Channappanavar R, Coleman C, Jiao J . Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016; 8(326):326ra21. DOI: 10.1126/scitranslmed.aaf1061. View

17.

Satterfield-Nash A, Kotzky K, Allen J, Bertolli J, Moore C, Pereira I . Health and Development at Age 19-24 Months of 19 Children Who Were Born with Microcephaly and Laboratory Evidence of Congenital Zika Virus Infection During the 2015 Zika Virus Outbreak - Brazil, 2017. MMWR Morb Mortal Wkly Rep. 2017; 66(49):1347-1351. PMC: 5730218. DOI: 10.15585/mmwr.mm6649a2. View

18.

Sejvar J . West Nile Virus Infection. Microbiol Spectr. 2016; 4(3). DOI: 10.1128/microbiolspec.EI10-0021-2016. View

19.

Clancy C, Van Wettere A, Siddharthan V, Morrey J, Julander J . Comparative Histopathologic Lesions of the Male Reproductive Tract during Acute Infection of Zika Virus in AG129 and Ifnar Mice. Am J Pathol. 2018; 188(4):904-915. PMC: 5955007. DOI: 10.1016/j.ajpath.2017.12.019. View

20.

Gardner C, Sun C, Luke T, Raviprakash K, Wu H, Jiao J . Antibody Preparations from Human Transchromosomic Cows Exhibit Prophylactic and Therapeutic Efficacy against Venezuelan Equine Encephalitis Virus. J Virol. 2017; 91(14). PMC: 5487544. DOI: 10.1128/JVI.00226-17. View