Exploration of immunoglobulin responses after influenza virus exposure

Every year billions of people get infected with the influenza virus, which results in three to five million cases of severe illness and hundreds of thousands of deaths due to respiratory complications. Though vaccines are available and given annually, they provide in some cases poor protection against infection and disease. Apart from that the virus mutates. Therefore, better vaccines that provide long-term or even lifelong protection to all influenza virus strains need to be developed. In this thesis we studied the antibody response against one of the major vaccine targets of influenza, namely the surface protein hemagglutinin (HA). We did this in non-human primates, because there the effect of different vaccination strategies can be studied and followed in a controlled setting. This is difficult to do in humans, since it is impossible to know the exact infection and/or vaccination history. We monitored the antibody response after a primary exposure to influenza virus in cynomolgus macaques (Macaca fascicularis) by using laboratory-made recombinant HA-proteins. We show that broad, potentially protective, antibody responses are formed early after experimental infection, but that these decrease in time. Vaccination might also induce these protective responses prior to infection, which are further enhanced after subsequent infection. However, also these broad responses are transient and seem to involve different immune pathways as induced by the more general influenza strain specific, but narrow, antibody responses. This research yielded important findings about the response after the infection, but also insights into the antibody (immunoglobulin) repertoire.