Summary
A bioRxiv preprint reports that mutations tuning complement activity changed how selected monoclonal antibodies protected neonatal mice from lethal HSV-1 infection. The effects varied with the antibody and its viral target.
A bioRxiv preprint reports that changing complement activity altered the protection provided by selected monoclonal antibodies in neonatal mice challenged with lethal herpes simplex virus type 1 (HSV-1). The effects differed across antibodies and their viral targets, rather than following a uniform pattern. The findings come from a mouse infection model, not a human study.
How the researchers altered antibody activity
The team tested monoclonal antibodies directed at two HSV-1 surface proteins, glycoprotein D and glycoprotein B. They modified each antibody’s Fc region—the part that can engage components of the immune system—using one of two mutations: E430G, described as complement-enhancing, or K322A, described as complement-abrogating.
Complement is a group of immune proteins that can help identify and damage pathogens. C1q is a recognition component of the classical complement pathway; its interaction with antibodies bound to a target can initiate that pathway. The preprint examines how this complement activity contributes to antibody-mediated antiviral protection.
In laboratory tests, the Fc modifications preserved the antibodies’ recognition of their viral targets while selectively increasing or reducing complement activity. The researchers then assessed protection in a neonatal mouse model of HSV-1 infection.
Protection depended on the antibody and target
Altering complement activity changed the protective capacity of some antibodies during lethal HSV-1 challenge. The direction and extent of the effect varied across the antibody panel and depended on the antibody and antigen involved. The results therefore point to complement as one contributor to antibody protection, working alongside antibody-specific properties rather than acting as a universal measure of effectiveness.
The study suggests that engineering an antibody’s Fc region could be a way to adjust complement-dependent activity. Whether that approach can improve antibody treatments for people with HSV-1 infection will require evidence beyond this neonatal mouse model. The work is posted as a preprint, and the supplied abstract does not report animal counts or quantitative effect sizes.