Profiling the Efficacy of CR1- Monoclonal Antibody Series Against New World Arenaviruses

Abstract Background Junín virus (JUNV) is the causative agent of Argentine Hemorrhagic Fever (AHF) with the capacity for human-to-human transmission. AHF is endemic to Argentina and is prevented in at-risk populations with the regionally approved Candid#1 live attenuated vaccine (JUNV/C#1). However, there are barriers to US FDA (Federal Drug Administration) or EMA (European Medicines Agency) licensure of JUNV/C#1, and there are no approved post-exposure medical countermeasures (MCMs). The CR1-series of monoclonal antibodies (mAbs), isolated from JUNV/C#1 recipients by the Abraham lab (Clark et. al, 2018) have been proposed as MCMs for the treatment of AHF. Methods Several of these antibodies were evaluated here for potential cross-protection to other pathogenic New World Arenaviruses (NWAV) by binding, mutational scanning, and chimeric virus neutralization assay. Protective efficacy against challenge with authentic JUNV was determined by prophylactic administration in a guinea pig model of AHF. Results Although mAb cross-binding to the soluble receptor binding domain of the viral glycoprotein (sGP1) from multiple strains of JUNV, and the related hemorrhagic fever causing NWAV, Machupo (MACV) was observed, these mAbs did not cross bind other NWAVs: Guanarito (GTOV), Sabia (SABV), and Chapare (CHAPV). The Hartley outbred guinea pig model of AHF was used to demonstrate the protective efficacy of CR1-28 for the prevention of AHF-like disease. Conclusions This study provides the first proof-of-concept evidence for mAb prophylaxis of AHF. However, the results also demonstrated that CR1-10 is not protective as a monotherapy.