The barrier effect of high-affinity IgM neutralizing antibodies provides enhanced blockage against rabies virus transport and infection

Abstract

Antibody-mediated protection plays a crucial role in post-exposure prophylaxis against rabies infection, while engineered antibodies with novel functional mechanisms offer enhanced preventive efficacy. In this study, we investigated the in vitro and in vivo activities as well as the protective efficacy of CR4008 antibodies with different conformational structures. We demonstrated that under passive immunization with antibodies of equivalent neutralizing efficacy, IgM antibodies exhibited superior protection against viral challenge compared with other antibodies. The underlying mechanism involves antibody barriers along the sarcolemma by IgM antibodies, which effectively inhibits viral transport in the infectious microenvironment within muscle tissues. Following high-affinity binding and neutralizing, barrier antibodies prevent the virus from retrogradely spreading to the central nervous system and prevent rabies development. Our study suggests that, in addition to neutralizing activity, effective inhibition of viral spread caused by the unique distribution of Immunoglobulin M (IgM) antibodies in exposed tissues is critical and valuable for passive immunization against rabies infection.