Childhood imprinting with broadly reactive influenza vaccines and their impact on establishing memory B cell populations 3758

Description Influenza vaccination early in life establishes memory B cell populations that are recalled upon future exposure to antigenically distinct influenza viruses. However, standard of care influenza vaccines typically elicit antibodies that are specific to the wild-type antigens in the vaccine, and generally do not offer broad protection against antigenically drifted viruses. To combat this, our laboratory has developed a methodology for generating computationally optimized broadly reactive antigens (COBRAs) for influenza hemagglutinin (HA). These antigens contain immunogenic epitopes from a multitude of co-circulating viruses to enhance antibody cross-reactivity. In this study, we compared the differences in polyclonal antibody reactivity and B cell repertoire diversity elicited in juvenile ferrets that were imprinted with either COBRA or wild-type HA vaccines. Sera collected from COBRA HA vaccinated juvenile ferrets had antibodies with broad hemagglutination inhibition (HAI) activity and the ability to neutralize H1N1 and H3N2 influenza viruses from multiple co-circulating clades. COBRA HA vaccinated animals also had more B cell clonal diversity than wild-type vaccinated animals following vaccine imprinting and exposure to antigenically drifted influenza viruses. Overall, juvenile ferrets imprinted with broadly reactive vaccines have diverse populations of memory B cells that recognize a multitude of influenza viruses, setting these animals up for a lifetime of protection. Funding Sources This project was funded by the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under contract 75N93019C00052. Topic Categories Vaccines and Immunotherapy (VAC)