Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies

Abstract

Viral diseases represent a major public health concerns and ever-present risks for developing into future pandemics. Antiviral antibody therapeutics, either alone or in combination with other therapies, emerged as valuable preventative and treatment options, including during global emergencies. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well-suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

Human antibodies neutralizing the alpha-latrotoxin of the European black widow

“…In this study, we therefore developed recombinant human antibodies that neutralize α-LTX and have a potential for the use as a therapeutic alternative to equine antivenom, but also as a diagnostic and research agent. In contrast to standardly used antivenom, human recombinant antibodies are sequence-defined, the production is long-term reproducible in mammalian cell culture and do not exhibit shelf-life issues due to the possibility of lyophilization ( 31 , 53 ) and represent a non-animal derived alternative ( 35 ). Employing different antibody phage display strategies, a total of 75 unique human antibodies binding L. tredecimguttatus α-LTX were selected from the naïve libraries HAL9 (lambda)/10 (kappa) ( 63 ).…”

“…The administration of foreign proteins naturally imposes an inherent risk of allergic reactions and serum sickness ( 26 , 29 – 31 ). Risk can be reduced, e.g.…”

Nanoluciferase Reporter Zika Viruses as Tools for Assessing Infection Kinetics and Antibody Potency

“…For antibody antiviral products, such as anti-ZIKV therapies, potency assays are most often neutralization assays of infectious virus in susceptible cell lines. As reviewed recently [8], neutralization assays can be performed with infectious viruses derived from clinical cases and propagated in the lab, pseudotyped virions (also called chimeric viruses), or replication-incompetent infectious particles (also called virus-like particles). For rapid and high-throughput assays, it is often desirable to use genetically modified viruses that express a reporter gene, while retaining infectivity and viral tropism.…”

DataSheet_1.pdf

“…In this study, we therefore developed recombinant human antibodies that neutralize a-LTX and have a potential for the use as a therapeutic alternative to equine antivenom, but also as a diagnostic and research agent. In contrast to standardly used antivenom, human recombinant antibodies are sequence-defined, the production is long-term reproducible in mammalian cell culture and do not exhibit shelf-life issues due to the possibility of lyophilization (31,53) and represent a non-animal derived alternative (35). Employing different antibody phage display strategies, a total of 75 unique human antibodies binding L. tredecimguttatus a-LTX were selected from the naïve libraries HAL9 (lambda)/10 (kappa) (63).…”

“…The administration of foreign proteins naturally imposes an inherent risk of allergic reactions and serum sickness (26,(29)(30)(31). Risk can be reduced, e.g.…”