Candidate for Universal Flu Vaccines Blocks Two Key Viral Proteins

Antibodies currently under study as candidates for a universal flu vaccine inhibit a second viral protein in addition to the one they bind, enhancing antibody neutralization of the virus and activation of immune cells, according to a new study. The research is being conducted by scientists at the National Institutes of Health and the recent findings were published today in the Journal of Experimental Medicine.

The candidate antibodies are known to bind the viral surface protein hemagglutinin, which mediates virion attachment and fusion with host cell membranes. Hemagglutinin consists of a head domain, containing the receptor binding site, and a stem domain that connects the head to the virion membrane. The head domain, which is prone to mutation, is targeted by current flu vaccines. The stem domain is far more resistant mutations, providing a target for universal flu vaccines.

In the current study, it was revealed that not only can stem-binding antibodies can block viral entry into host cells by inhibiting hemagglutinin cell fusion activity, they also inhibit an enzyme called neuraminidase. Neuraminidase also resides on the surface of the influenza virus and its role is to release budding progeny virions form the cell surface that remain attached via hemagglutinin binding.

Experiments in mice further confirmed the ability of anti-stem antibodies to inhibit neuraminidase and prevent flu symptoms. "The ability of neuraminidase inhibitors to enhance... immune cell activation [by anti-stem antibodies] bound to viruses or infected cells suggests the possible clinical synergy between neuraminidase inhibitors and [anti-stem antibodies] in humans," the authors write.

These findings could help researchers in future vaccine development efforts.

Image: Cryo-electron microscopy shows spikes of hemagglutinin and neuraminidase projecting from the surface of influenza A viruses. Image courtesy of Kosik et al., 2019