Maltseva, Mariam2025-01-212025-01-212025-01-21http://hdl.handle.net/10393/50121https://doi.org/10.20381/ruor-30879The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of highly transmissible variants of this virus have significantly impacted the effectiveness of vaccines against infection, COVID-19 disease outcomes, and transmission. The decline in vaccine efficacy can be attributed to several factors, including immune evasion by new variants, waning immunity over time post-vaccination or infection-acquired immunity, and inadequate induction of protective mucosal immunity. While booster vaccinations have notably enhanced protection against severe disease, the continuous evolution of the virus necessitates a re-evaluation of current vaccine strategies due to their inherent limitations to prevent new infections. To address these challenges effectively, it is crucial to consider the viral life cycle, accurately characterize viral phenotypes, and understand the interactions between the virus and the host, as well as the resulting immunological responses. This thesis explores virus-host interactions by characterizing viral phenotypes using flow virometry techniques and investigates viral kinetics, alongside the modulation of the host's immune response following viral infection. By analyzing these interactions, we aim to refine vaccine design and delivery, advancing the development of next-generation vaccines against SARS-CoV-2 and other respiratory viruses. This doctoral thesis examines different immunization regimens and vaccine formulations, characterizing the humoral responses across various anatomical and immunological compartments. My research identifies immunogenic targets for intranasal vaccine design against SARS-CoV-2 and explores the impact of different vaccine formulations on induced humoral responses, providing insight into the development of a universal vaccine platform. Robust and durable mucosal immunity is crucial for neutralizing viruses and limiting infection at the point of entry. Lastly, a plant-based expression platform for producing vaccine antigen candidates was evaluated, highlighting plant-produced proteins as advantageous candidates for use in protein subunit vaccines. Our data supports that the mucosal humoral response to SARS-CoV-2 intranasal vaccination is relevant to the development of more effective next-generation vaccine strategies to combat SARS-CoV-2 and other respiratory pathogens.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/SARS-CoV-2CoronavirusesMucosal ImmunologyVaccinesFlow VirometryNanoscale Flow CytometryRespiratory VirusesThesis