Identification of antibodies to target the NA globular head domain

National Institute of Health (NIH) scientists have discovered antibodies targeting the underside of the neuraminidase (NA) globular head domain. The (NA) protein is common among many influenza viruses, including H3N2 subtype viruses.

Millions of people globally become sick from influenza. Although vaccination reduces the burden of the disease, updated vaccines are required each season to provide protection against multiple strains and subtypes of the evolving virus. Producing a vaccine that protects against a broad range of influenza viruses could stop outbreaks of new viruses without the need for yearly vaccine reformulation.

One method to improve influenza vaccines is to find novel targets on the virus’ surface proteins in conserved regions. Influenza NA is a surface protein containing a globular head portion and a narrow stalk portion. The underside of the NA head has a highly conserved region with epitopes that make it vulnerable to antibody binding and inhibition to the virus. It also is not impacted by mutations common in drug-resistant strains.

The team isolated human antibodies, that target the underside of the NA head, from the blood of two people who had recovered from influenza type A subtype H3N2.  In lab tests, the antibodies inhibited propagation of viruses from subtype H2N2, and H3N2 viruses from humans, swine, and birds. Also, they protected mice from lethal infection by a subtype H3N2 virus when administered either one day before or two days after infection, demonstrating that the antibody could treat and prevent influenza in this model. 

Using cryogenic electron microscopy, the researchers analysed the structure of two of the antibodies while bound to NA. Each antibody targeted different, nonoverlapping regions of the NA head underside, showing that this region has multiple areas that may be useful to explore for countermeasure development. 

The study’s results indicate that antibodies targeting the NA head underside could be useful in combination with antivirals or other types of antibodies to combat influenza, as they are effective against influenza viruses with drug-resistant mutations. Also, NA head underside targets could be included in the next generation of broadly protective vaccines against influenza.

This study was published in Immunity.