N1 neuraminidase monoclonal antibodies 2H08 and 3H03 have decreased binding and inhibition properties against H1N1 influenza viruses circulating after 2018

Abstract

Influenza viruses are global public health problem. Vaccines are available but have to be updated annually due to antigenic drift of the main vaccine component, the surface glycoprotein hemagglutinin (HA). The second surface glycoprotein of the virus, neuraminidase (NA), has recently moved into the spotlight of vaccine development. However, its antigenic evolution is understudied. We found that two broadly protective N1 NA antibodies, which had previously been shown to bind and inhibit most N1 NA, lost activity to recent N1s from seasonal H1N1 viruses. Here, we show that this drop in activity can mostly be attributed to a change in electrostatic surface potential from neutral to positively charged. This effect was not observed when historic human plasma samples were tested, suggesting that the drop of activity is specific to the two tested mAbs but does not broadly impact the polyclonal human response. Finally, we confirmed that the tested mAbs were fully active against recently emerged pan-zootic clade 2.3.4.4b H5N1 NA.