International Society for Disease Surveillance Conference 2011: Building the Future of Public Health Surveillance: Building the Future of Public Health Surveillance

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-04204pubpub1117

Emerg Infect Dis

Emerging Infectious Diseases is providing access to these abstracts on behalf of the ICEID 2022 program committee (http://www.iceid.org), which performed peer review. ICEID is organized by the Centers for Disease Control and Prevention and Task Force for Global Health, Inc.Emerging Infectious Diseases has not edited or proofread these materials and is not responsible for inaccuracies or omissions. All information is subject to change. Comments and corrections should be brought to the attention of the authors.Suggested citation: Authors. Title [abstract]. International Conference on Emerging Infectious Diseases 2022 poster and oral presentation abstracts. Emerg Infect Dis. 2022 Sep [date cited]. http://www.cdc.gov/EID/pdfs/ICEID2022.pdf2022PMC94238981187

Immune response to influenza after vaccination and infection

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

The antigenic evolution of human influenza A haemagglutinin

A detailed understanding of the B-cell response to influenza A haemagglutinin is key to the accurate matching of vaccines to seasonal strains, and may inform the development of broader spectrum vaccines. In this study, I develop techniques for predicting the location of the epitopes of protective antibodies by observing the physical locations of amino acid substitutions in human wild-type strains. By linking the understanding gained from this analysis with a large body of assay data, I present a model which can predict antigenic distance from HA1 amino acid sequences and which meets or exceeds the predictive power of previously developed models while retaining generality. An interesting conclusion from the epitope analysis discussed above is that antibodies to the HA head bind in two regions. The antigenic evolution of influenza H3N2 is more punctuated than its genetic evolution. I propose that the dual regions might contribute to the punctuated nature of antigenic evolution, and explore this through the use of a simple simulation. Stalk-binding antibodies to HA have attracted much interest in recent years: a number of broad-binding examples have been isolated, and the slower evolution of the stalk gives hope that these may provide broad protection against future strains. Stalk-binding neutralising antibodies to H3 are known to bind in two regions, and I use data from crystal studies to identify the constituent residues of these regions, which I term antigenic sites F and G, in a manner that is consistent with previous analyses of the constituent residues of HA1 antigenic sites A-E. I analyse the degree of conservation of residues in sites F and G, and conclude that there have been episodes of change in the H3 stalk which are consistent with antigenic evolution