Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies

Publication date: 5 April 2018 Source:Cell, Volume 173, Issue 2 Author(s): Yao-Qing Chen, Teddy John Wohlbold, Nai-Ying Zheng, Min Huang, Yunping Huang, Karlynn E. Neu, Jiwon Lee, Hongquan Wan, Karla Thatcher Rojas, Ericka Kirkpatrick, Carole Henry, Anna-Karin E. Palm, Christopher T. Stamper, Linda Yu-Ling Lan, David J. Topham, John Treanor, Jens Wrammert, Rafi Ahmed, Maryna C. Eichelberger, George Georgiou, Florian Krammer, Patrick C. Wilson 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 ...
Source: Cell - Category: Cytology Source Type: research