Two broadly neutralizing monoclonal antibodies, DC2.M16 and DC2.M357, isolated from a convalescent donor, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice.
Near-germline human monoclonal antibodies isolated from a CHIKV-convalescent donor can broadly neutralize and protect against multiple arthritogenic alphaviruses in mice.
Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline-revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections.
Malonis et al. (Fri,) conducted a other in Arthritogenic alphavirus infection (CHIKV, MAYV) (n=1). Broadly neutralizing monoclonal antibodies (DC2.M16 and DC2.M357) was evaluated on Neutralization of alphaviruses and protection against musculoskeletal disease in mice. Two broadly neutralizing monoclonal antibodies, DC2.M16 and DC2.M357, isolated from a convalescent donor, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice.