Universal Antibody Targeting the Highly Conserved Fusion Peptide Induces Antibody-Dependent Cellular Cytotoxicity Against Diverse Strains of Both Influenza Types A and B Viruses

Abstract

Influenza is a major public health concern causing millions of hospitalizations every year. Either type A (IAV) or B (IBV) viruses can cause the diseases. While IAV is generally the predominant circulating virus, IBV can be more dominant than IAV in a given season. The current seasonal vaccines need to be updated annually based on prediction of the likely strains in the upcoming season. However, mismatches between vaccine strains and the actual circulating viruses can occur because of the remarkably high rate of mutation in the viral surface glycoprotein, hemagglutinin (HA), reducing vaccine effectiveness significantly. HA consists of two subunits, HA1 and HA2, where HA1 evolves in an unpredictable fashion while HA2 is highly conserved. Previously, we identified a 14-aa fusion peptide sequence at the N-terminus of HA2 that is universally conserved in IAV and IBV. Antibody against this epitope was able to bind and quantify multiple influenza viruses as well as cross-neutralize multiple subtypes of IAV. Here, we show that the universal antibody induces robust antibody-dependent cellular cytotoxicity (ADCC) against diverse influenza viruses, including human and avian IAVs as well as both lineages of IBV. These results revealed the versatile effector functions of this universal antibody.

Funding Information: This work was supported by the Government of Canada.

Declaration of Interests: The authors declare no conflict of interest.

Keywords: influenza, universal antibody, Uni-1, antibody-dependent cellular cytotoxicity (ADCC)