B cell immunity to the Lassa virus glycoprotein is a correlate of vaccination-induced virus control in mice.

Lassa fever, a viral hemorrhagic fever caused by the arenavirus Lassa virus (LASV), affects thousands of individuals annually, highlighting the need for a vaccine. Yet, immunological correlates of viral load control remain poorly defined. Here we study vaccination-induced immunity in a surrogate LASV challenge model in mice. We find that LASV-cross-reactive B cell immunity induced by the glycoprotein of distantly related arenaviruses, such as lymphocytic choriomeningitis virus (LCMV), provides significant viral load control. Counter to common concepts, suppression of viremia is observed in the absence of CD8 T cells or neutralizing antibodies but correlates with non-neutralizing glycoprotein-specific antibody responses. Adoptive cell transfer experiments with monoclonal LCMV-specific B cells demonstrates that these cells suppress viral loads when previously activated by a heterologous cross-reactive glycoprotein and diversified by somatic hypermutation. These findings establish vaccination-induced B cell immunity to the LASV glycoprotein as a correlate of viral load control, independently of virus-neutralizing antibody titers at the time of challenge.