Cross-Reactive Antibodies Binding to the Influenza Virus Subtype H11 Hemagglutinin

Abstract

H11 subtype influenza viruses were isolated from a wide range of bird species and one strain also was isolated from swine. In an effort to generate reagents for a chimeric H11/1 hemagglutinin-based universal influenza virus vaccine candidate, we produced 28 monoclonal antibodies that recognize the H11 HA subtype. Here we characterized these antibodies in terms of binding breadth and functionality. We found that the antibodies bind broadly to North American and Eurasian lineage isolates and also show broad neutralizing activity, suggesting that immunogenic epitopes on the H11 head domain are not under strong pressure from immunity in the natural reservoir. Furthermore, we found that the antibodies were highly hemagglutination inhibition active against the homologous chimeric H11/1N1 virus, but approximately 50% lost this activity when tested against a virus expressing the same the full length H11 HA of which the head domain is present on cH11/1 HA. Furthermore, while strong neutralizing activity was found to a genetically distant North American lineage H11 isolate, little hemagglutination inhibition activity was detected. This suggests that small structural changes between wild type H11 and cH11/1 as well as between Eurasian and North American lineage H11 HAs can strongly influence the functionality of the isolated monoclonal antibodies.