Single domain antibody multimers confer protection against rabies infection

Boruah, Bhargavi M., Liu, Dawei, Ye, Duan, Gu, Tie-jun, Jiang, Chun-lai, Qu, Mingsheng, Wright, Edward, Wang, Wei, He, Wen, Liu, Changzhen and Gao, Bin (2013) Single domain antibody multimers confer protection against rabies infection. PLoS ONE, 8 (8). e71383 1-10. ISSN 1932-6203

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Abstract

Post-exposure prophylactic (PEP) neutralizing antibodies against Rabies are the most effective way to prevent infection-related fatality. The outer envelope glycoprotein of the Rabies virus (RABV) is the most significant surface antigen for generating virus-neutralizing antibodies. The small size and uncompromised functional specificity of single domain antibodies (sdAbs) can be exploited in the fields of experimental therapeutic applications for infectious diseases through formatting flexibilities to increase their avidity towards target antigens. In this study, we used phage display technique to select and identify sdAbs that were specific for the RABV glycoprotein from a naïve llama-derived antibody library. To increase their neutralizing potencies, the sdAbs were fused with a coiled-coil peptide derived from the human cartilage oligomeric matrix protein (COMP48) to form homogenous pentavalent multimers, known as combodies. Compared to monovalent sdAbs, the combodies, namely 26424 and 26434, exhibited high avidity and were able to neutralize 85-fold higher input of RABV (CVS-11 strain) pseudotypes in vitro, as a result of multimerization, while retaining their specificities for target antigen. 26424 and 26434 were capable of neutralizing CVS-11 pseudotypes in vitro by 90–95% as compared to human rabies immunoglobulin (HRIG), currently used for PEP in Rabies. The multimeric sdAbs were also demonstrated to be partially protective for mice that were infected with lethal doses of rabies virus in vivo. The results demonstrate that the combodies could be valuable tools in understanding viral mechanisms, diagnosis and possible anti-viral candidate for RABV infection.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QR Microbiology > QR0355 Virology
Depositing User: Edward Wright
Date Deposited: 14 Aug 2018 09:10
Last Modified: 02 Jul 2019 14:51
URI: http://sro.sussex.ac.uk/id/eprint/77824

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