Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity

Abstract

Targeting multiple viral proteins is pivotal for sustained viral suppression. In recent years, several broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed. However, the impact of dual neutralization of these two glycoproteins on the course of infection has not been thoroughly tested. Here we demonstrate that a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase has a dual antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We further show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over antibody combination as it results in an improved neutralization capacity and augmented antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice. These findings suggest that dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.