Abstract
Broadly-neutralizing monoclonal antibodies are of high therapeutic utility against infectious diseases caused by bacteria and viruses, as well as different types of intoxications. Snakebite envenoming is one such debilitating pathology, which is currently treated with polyclonal antibodies derived from immunized animals. For the development of novel envenoming therapies based on monoclonal antibodies with improved therapeutic benefits, new discovery approaches for broadly-neutralizing antibodies are needed. Here, we present a methodology based on phage display technology and a cross-panning strategy that enables the selection of cross-reactive monoclonal antibodies that can broadly neutralize toxins from different snake species. This simple in vitro methodology is immediately useful for the development of broadly-neutralizing (polyvalent) recombinant antivenoms with broad species coverage, but may also find application in the development of broadly-neutralizing antibodies against bacterial, viral, and parasitic agents that are known for evading therapy via resistance mechanisms and antigen variation.
Highlights
Broadly-neutralizing monoclonal antibodies are of high therapeutic utility against infectious diseases caused by bacteria and viruses, as well as different types of intoxications
By developing and applying a phage display methodology relying on cross-panning against two different CTxs (Fig. 1a), we demonstrate the feasibility of discovering broadly-neutralizing human monoclonal antibodies capable of neutralizing CTxs from the venoms of three different cobras
Collected fractions were dried in a vacuum centrifuge, dissolved in phosphate buffered saline (PBS), pooled, and concentrations were estimated at 280 nm (NanoDrop OneC Spectrophotometer, Thermo Scientific)
Summary
Broadly-neutralizing monoclonal antibodies are of high therapeutic utility against infectious diseases caused by bacteria and viruses, as well as different types of intoxications. We present a methodology based on phage display technology and a cross-panning strategy that enables the selection of cross-reactive monoclonal antibodies that can broadly neutralize toxins from different snake species. Antivenoms containing animal-derived polyclonal antibodies are the only effective therapy against this debilitating condition Many of these medicines have limited neutralization capacity against the venoms that they are indicated for. Necrotic regions, but does not reduce the necrotic area in mice[11] For this reason, and in pursuit of developing a systematic methodology for discovering broadly-neutralizing antibodies against snake toxins, we chose to focus on CTxs obtained from African cobras as model antigens. By developing and applying a phage display methodology relying on cross-panning against two different CTxs (Fig. 1a), we demonstrate the feasibility of discovering broadly-neutralizing human monoclonal antibodies capable of neutralizing CTxs from the venoms of three different cobras. We thereby show that by strategically selecting which venom toxins to be used as antigens, we can select monoclonal antibodies that are able to neutralize the CTxs employed as antigens, and homologous CTxs from venoms of different snake species
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