Universität Tübingen
Post-Pandemic Serosurveillance of RSV and Influenza: Development and Application of Multiplex Immunoassays
Abstract
With seasonal epidemics each year and several global pandemics, respiratory viruses represent a significant global health burden. Respiratory syncytial virus (RSV) and Influ- enza viruses are of particular concern as they have a severe impact on vulnerable popu- lations such as infants and the elderly and can trigger global pandemics through antigenic drift or zoonotic transmission. The disruption of viral seasonality caused by the SARS- CoV-2 pandemic has hampered continuous epidemiologic surveillance and highlighted the need for reliable serologic tools to assess immunity and infection status at the popu- lation level in times of limited clinical surveillance. The aim of this thesis was to develop and validate two antibody binding multiplex immu- noassays, RSV MIA and FLU MIA, that enable sensitive and subtype-resolved detection of virus-specific antibody responses in both serum and other sample matrixes. These as- says were then used to generate population-level serological data on RSV and Influenza immunity and infections within a longitudinal retrospective cohort study. The assays were then also used to investigate vaccine-induced immune responses, such as Influenza an- tibodies produced in an organ-on-chip model system. To achieve this, I developed and validated the RSV MIA and the FLU MIA according to EMA and FDA guidelines, enabling robust high-throughput quantification of antigen-specific antibody titers. To determine assay performance and to understand the immune response to an RSV/Influenza infec- tion, both assays were clinically validated using samples from human challenge studies. When used in a longitudinal population cohort study, RSV MIA could be used to identify seasonal RSV infections, often including the viral subtype. FLU MIA showed high sensitiv- ity in detecting broad and strain-specific humoral responses after both influenza vaccina- tion and seasonal infection, including seasonal patterns induced by circulating influenza strains between years. In the organ-on-chip system, FLU MIA successfully quantified an- tigen-specific antibodies in response to vaccine administration, confirming the ability of lymphoid tissue to elicit measurable immune responses ex vivo. Taken together, these re- sults underscore the versatility of both assays for seroepidemiologic studies and vaccine testing platforms. By enabling detailed analyses of infection- and vaccine-induced hu- moral immunity, these assays provide a valuable foundation for future epidemiologic sur- veillance and next-generation vaccine evaluation.
Author and committee
dc:creator, dc:contributor.*- Author
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- Marsall, Patrick
Identifiers
dc:identifier.*- Identifier
- hdl:10900/173305