The nature and evolution of humoral immune responses to influenza virus

Influenza epidemics and pandemics have been and will be a major public health problem. In the course of life, everybody experiences several infections with influenza virus. However, these infections provide insufficient immunity against new infections since the virus constantly changes. How consecutive infections shape our repertoire of influenza virus-specific antibodies and how this affects the response to a newly encountered virus strain is poorly understood. In this thesis we used blood samples from young, adult and elderly individuals from the Lifelines cohort to study the antibody responses to 5 influenza virus strains which circulated between 1934 and 2009. We observed that very potent but highly virus strain-specific antibodies were highest against a virus strain encountered early in life for all age groups. Yet, other antibodies, less potent but also less specific for a certain virus strain, were highest against recently encountered strains. We could show that these latter antibodies, so far often overlooked, could provide partial protection against infection with a new virus strain. Our observations imply that influenza vaccines should be designed to induce broadly reactive antibodies, even if moderately potent, to protect against newly emerging influenza virus strains.

Dissertation: http://hdl.handle.net/11370/a080a253-e083-4634-82eb-9ce35b69f011