A strategy to identify human monoclonal antibodies that neutralize a broad spectrum of influenza A subtypes (38.12)

Abstract

Influenza A continues to be a serious public health threat as it continuously evolves to evade and escape immune surveillance through genetic drift, shift, and re-assortment. Hemagglutinin (HA) is the main glycoprotein target of the humoral immune response and elicits protective, neutralizing, antibodies during infection. However, these antibodies are usually specific for the influenza subtype causing infection and exhibit a narrow spectrum of protectiveness. To date, many of the influenza-neutralizing monoclonal antibodies described are cross-specific for subtypes H1 and H5 but do not neutralize subtypes H3 or H7. Therefore, we have designed an approach to survey the human B cell repertoire to identify monoclonal antibodies that neutralize influenza viruses of both the H1 and H3 subtypes. Our strategy is to identify humans that have broadly reactive serum antibodies, culture IgG+ memory B cells from these individuals at near clonal density, and then assay the culture supernatants for the presence of antibodies that neutralize both H1 and H3 influenza subtypes. By combining functional and binding assays we will determine if there exist in nature highly conserved neutralizing epitopes that are represented on most or all of the influenza HA subtypes tested.