Discovery and characterization of potently neutralizing human monoclonal antibodies against Mayaro virus 4371

Abstract Description Alphaviruses are enveloped, single-stranded, positive-sense RNA viruses that cause acute and chronic arthralgia and myalgia, or encephalitic disease in humans, generating a global health impact. The emergence and re-emergence of alphaviruses with pandemic potential exist due to the geographical expansion of arthropod vectors, urbanization, and transmission potential. Mayaro virus (MAYV) is a zoonotic alphavirus with high pandemic potential and no approved human medical countermeasures. As such, MAYV was selected as a prototype pathogen for a proof-of-concept study to test and continually enhance our laboratory’s capabilities to identify, isolate, characterize, optimize, and produce a combinatorial therapy of potently neutralizing human monoclonal antibodies (mAbs) against a chosen target pathogen. Our discovery efforts have identified potently neutralizing anti-MAYV mAbs derived from naturally infected donors. Herein, we showcase the rapid and high-throughput discovery workflow of our laboratory, which reveals the binding, neutralization, structural, and protective characteristics of multiple candidate mAbs via in vitro and in vivo models. Furthermore, we have pinpointed viral escape mutations and potential mechanisms of neutralization evasion. By identifying mAbs that target conserved virus glycoprotein ectodomains, the candidates have high potential for human therapeutic use as prophylactic and post-exposure medical countermeasures. Topic Categories Vaccines and Immunotherapy (VAC)