Vaccination with computationally optimized broadly reactive antigens may preferentially recall influenza hemagglutinin-directed antibodies endowed with broadly neutralizing activity 2149

Description To develop vaccination strategies that can overcome antigenic drift, it is important to characterize and dissect the antibody response to influenza vaccine strains as well as to next-generation vaccines like Computationally Optimized Broadly Reactive Antigens (COBRA). Blood was sampled longitudinally before and after standard of care influenza vaccination of 15 individuals from different age groups for 4 consecutive influenza seasons. Binding and hemagglutination-inhibiting (HAI) antibody titers were determined against a large panel of historical, recent and next-generation influenza virus A and B hemagglutinins (HA) and strains. Monoclonal antibodies (mAbs) were isolated from these individuals, recombinantly expressed and evaluated for their breadth of binding and functional activity. Several individuals have outstanding breadth, showing protective responses against many strains, both at the polyclonal and mAb level. Of the 31 mAbs tested, 19 are broadly neutralizing, with some of them also showing heterosubtypic activity. Interestingly, these mAbs recognize and show HAI activity also against COBRA HA and viruses. A vaccine that preferentially elicits and boosts these antibodies could confer broadly protective immunity to influenza. In this study, a high antibody titer was observed against COBRA HA and, importantly, these antigens are also bound by broadly neutralizing antibodies, suggesting the possible elicitation and recall of these antibody populations by COBRA in humans. Funding Sources This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the U.S. National Institutes of Health (NIH), Department of Health and Human Services, under contract 75N93019C00052. Topic Categories Vaccines and Immunotherapy (VAC)