Dissecting the role of sex hormones in human antiviral immunity

COVID-19 severity and mortality are consistently higher in men than women. Still, the mechanisms that underlie sex differences in human antiviral immunity remain poorly understood. Therefore, investigating sex-specific regulation of immune responses is a critical step for developing novel and effective antiviral therapies. The overarching goal of SHIFT is to dissect the precise contribution of sex hormones to human antiviral immune function by studying the immune system of individuals as they undergo sex-reassignment therapy with sex hormones. The three specific aims proposed are 1) to evaluate the sex hormone contribution to viral infection susceptibility, 2) to characterize sex hormone effects on the immune-microbe interactions and balance, and 3) to assess sex hormone effects in antiviral immune responses during infection. SHIFT will combine the experienced researcher'Äôs advanced knowledge in sex hormone regulation of immune function and metabolism, with the host lab'Äôs state-of-the-art multi-omics technologies, advanced expertise in systems immunology analysis and established collaborations in Sweden. Aims will be achieved during a planned 24-month training at Karolinska Institutet that involve technical training (sample collection and processing), analytical training (integrative computational analysis and statistics), and development of transferrable skills (project management, mentoring, leadership and communication). The two-way transfer of knowledge in SHIFT will lead to implementation of new techniques, mentoring of trainees, and identification of sex-hormone regulated pathways in antiviral immunity that will be valuable for vaccine design, antiviral therapies and immunomodulatory therapies at large. Further, the MSCA fellowship will provide a strong training path in systems immunology to lead the fellow towards academic independence in the EU and support her career goals of becoming an investigator studying immunological basis of disease susceptibility.