High-titer convalescent serum from cats recovered from severe fever with thrombocytopenia syndrome protects SFTSV-infected mice

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, tick-borne zoonosis caused by severe fever with thrombocytopenia syndrome virus (SFTSV) and is associated with high case-fatality rates in humans and cats. No vaccines or antiviral drugs are currently available for the prevention or treatment of feline SFTS. Because cats with SFTS often develop blood viral RNA loads exceeding those in severe human cases, we hypothesized that some naturally recovered cats develop strong neutralizing antibody responses and may serve as a potential source of antibody-rich serum for passive immunotherapy. We compared 80% plaque-reduction neutralization test (PRNT80) titers in convalescent sera from six human SFTS survivors and 14 cats that had recovered from naturally acquired SFTS, then evaluated the therapeutic efficacy of convalescent cat serum in SFTSV-infected, interferon receptor-deficient AG129 mice. Some SFTS-recovered cats showed high PRNT80 titers. Passive administration of high-titer convalescent cat serum early after infection protected SFTSV-infected mice. A single dose given at 2 or 3 days post-infection completely protected mice, whereas treatment at 4 days post-infection resulted in 40% survival. Administration on two consecutive days was associated with lower late-phase viremia in surviving mice. Sera from three independent SFTS-recovered cats improved survival, with greater effects observed for sera with higher neutralizing antibody titers. These findings indicate that some cats recovering from SFTS can develop high neutralizing antibody titers and their sera can exert therapeutic effects in an SFTSV-infected mouse model. These findings support further evaluation of passive immunotherapy as a treatment strategy for feline SFTS.