Recombinant snakebite antivenom for sub-Saharan Africa

Sub-Saharan Africa (sSA) is heavily burdened by snakebite envenoming. Existing antivenoms are scarce and many have suboptimal therapeutic properties. To improve snakebite envenoming therapy, the application of carefully designed mixtures of fully human monoclonal immunoglobulin G (IgG) antibodies for systemic and nanobodies for locally acting toxins poses as not only a therapeutically promising, but also scientifically feasible solution. Therefore, taking advantage of our well-established discovery pipelines and expertise in working with oligoclonal and broadly-neutralizing antibodies against toxins, we will develop a broad-spectrum (polyvalent) recombinant antivenom for sSA. The project will focus on the following technical goals that we believe have a potential to deliver measurable societal and humanitarian health impact: 1) The identification and isolation of all medically relevant snake venom toxins that need to be neutralized by a recombinant antivenom for sSA and 2) the discovery of a well-characterized panel of broadly-neutralizing IgGs and nanobodies that can neutralize all medically relevant systemically-acting and deep tissue penetrating toxins found in the 24 medically most relevant snake species from this region. Combined, these efforts will create a substantial shift in snakebite envenoming therapy and will enable the clinical development of improved, low-cost, and quality-assured snakebite therapeutics for victims in sSA.