Peripheral human mAb therapy yields modulation of neuroinflammation and long-term functional recovery from lyssavirus infection

We furthermore found that a single dose of either A6 or RVC20 protected animals from mortality induced by Australian bat lyssavirus (ABLV), while promoting substantial long-term functional recovery. Moreover, A6 similarly protected animals from mortality following infection with a currently circulating wild isolate of <i>rabies virus</i> (RABV). Transcriptomics analysis of brain RNA and protein-based analysis of brain tissue homogenates demonstrated that therapy with A6 broadly reduced expression of neuroinflammatory mediators during the acute phase of infection.

Interestingly, infection of animals with a non-lethal attenuated mutant of ABLV resulted in similar neuroinflammation. Thus, a robust neuroinflammatory response to ABLV does not predict mortality. Overall, peripheral therapy with A6 and similar neutralizing mAbs promotes survival and long-term functional recovery from CNS-resident lyssavirus infection in a manner that includes suppression of the G pre- to postfusion transition and modulation of neuroinflammation.</p>