Therap Human Monoclonal Antibod for Treatment of Hantavirus Cardiopulmonary Syndr

University Of California-Irvine, Irvine CA

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Abstract

An effective vaccine for the prevention of HCPS in the Americas has not been developed and treatment is limited to supportive care at present. Ribavirin, while effective at restricting viral replication in vitro, has not conclusively been shown to be efficacious in alleviating HCPS severity. A recent study of SNV-infected patients demonstrated that mild disease is significantly associated with high levels (>1:800) of anti-SN virus neutralizing (Nt) antibodies at the time of hospital admission(13). Furthermore, low titers (si :200) of Nt antibody at this same time point correlate with severe disease and high mortality. Indeed, administration of immune plasma from recovered HCPS patients to deer mice is sufficient to protect these reservoir rodents from viral challenge if it is administered prior to challenge (Rafael Medina and Brian Hjelle, unpublished data). In a separate study, ANDV-specific Nt antibodies (recovered from Rhesus macaques) were able to protect hamsters from lethal disease when passively administered(34). These antibodies were also able to cross-neutralize both SNV and Black Creek Canal virus (another HCPS agent in North America). In rodent models of SNV, Hantaan virus, Puumala virus (PUUV), and Seoul virus infection, maternally-acquired or passively transferred antibodies are sufficient to prevent infection and/or ameliorate disease(18, 21, 27, 37-39, 44, 71, 72, 82). Based upon these observations, we hypothesize that passive administration of Nt antibodies may be an effective therapeutic intervention to reduce/prevent morbidity and mortality due to HCPS disease resulting from infection with SNV and ANDV.