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

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.

Bovine-derived antibodies and camelid-derived nanobodies as biotherapeutic weapons against SARS-CoV-2 and its variants: A review article

“…These TcB's have limited long-term hyperimmunization, unlike vaccines, their adjuvants, or other immune stimulators. TcB's are currently used to produce fully human antibodies (polyclonal human IgG) against Hantavirus (HTNV) [ 65 , 66 ], Middle East Respiratory Syndrome coronavirus (MERS-CoV) [ 67 , 68 ], Ebola virus [ 69 ], Venezuelan equine encephalitis virus (VEEV) [ 70 ], Puumala virus (PUUV) [ 65 ] and Zika virus [ 71 , 72 ]. Recently, besides polyclonal antibodies, monoclonal antibodies have been produced in TcB against Influenza A Virus [ 73 ].…”

Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases

“…CP was tested and showed efficacy (Table 2); however, HIG offered several advantages as a sustainable therapeutic option to provide a bridge between the outbreak and vaccine availability and to be administered upon infection to deliver immediate protection. Therefore, development of HIGs was evaluated 100,[130][131][132] for prophylaxis of ZIKV infection in at-risk populations, including women of childbearing potential and pregnant women. ZIKV-HIG, manufactured from human plasma with high titers of anti-ZIKV antibodies, was shown to prevent and/or neutralize ZIKV infection in preclinical studies using an immune-deficient mouse model (Ifnar1 -/-).…”

Bovine-Origin Human Therapy; Need More Attention

“…This study demonstrated an efficacy in vitro and in a mouse model of MERS-CoV infection showing how large quantities of human MERS-CoV-neutralizing antibodies can be rapidly produced in Tc bovines, providing a possible strategy for the development of passive immunotherapy against coronaviruses or other new and emerging infectious diseases 26 . Fully human polyclonal antibodies, produced in TcB, can be elicited against many viruses [26][27][28][29][30][31][32] (Ebola Zaire Virus) and some of them have already been shown to be safe and effective in human clinical trials 30,33 .…”