Immune response to influenza after vaccination and infection

Abstract

Influenza causes great human morbidity and mortality from annual epidemics and pandemics occurring at irregular intervals. The socioeconomic impact of influenza is significant with 5% of adults and 20% of children infected, and 500 000 fatal cases globally each year. Elderly have the highest risk of fatal disease, while children are main transmitters of the virus and the youngest are most often hospitalized. Influenza is a vaccine preventable disease, but the vaccines require annual updating due to constant viral mutations, and they are only moderately effective. The immune system is vital in clearing influenza illness, and the mechanisms behind the complex immune response to the virus are not clear. Increased knowledge of these responses is required for the development of the much needed, improved future influenza vaccines. In this doctoral work we investigated the immunological mechanisms elicited in both vaccinated children and influenza infected adults. Two clinical studies were conducted and immune responses analysed. Firstly, we investigated the immunogenicity after vaccination with a live attenuated influenza vaccine (LAIV) in 55 children and controls. Evidence of early and durable LAIV induced responses was found in saliva, blood and tonsils, with responses both in the cellular and humoral immune compartments. This indicates a broad, protective response, where especially cellular responses are interesting. To our knowledge we are the first to show tonsillar responses after LAIV, and lasting cellular responses, up to one year. Saliva IgA is suggested as a possible, non-invasive correlate of immunogenicity after LAIV.

Secondly, we dissected the immunological responses in adults infected during the 2009 influenza pandemic. Patients in the acute phase showed low levels of CD8+ T-cells compared to convalescent patients, and those with severe disease showed the highest levels of antibodies. CD8+ T-cells are vital for viral clearance, however there are few reports on responses from naturally infected patients. Differences in T-cell subsets may define disease severity. The multifaceted immune response induced by vaccination or infection indicates that T-cells are important in the immune defence against influenza and are therefore ideal targets for future influenza vaccines.