Paper of the Month April 2018
Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies
Cell. 2018 Apr 5;173(2):417-429.e10.
Chen YQ, Wohlbold TJ, Zheng NY, Huang M, Huang Y, Neu KE, Lee J, Wan H, Rojas KT, Kirkpatrick E, Henry C, Palm AE, Stamper CT, Lan LY, Topham DJ, Treanor J, Wrammert J, Ahmed R, Eichelberger MC, Georgiou G, Krammer F, Wilson PC.
Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.