Understanding transgender women's immune and behavioral responses to seasonal COVID-19 vaccines to improve their uptake - Sex differences in immunity are dynamic throughout the lifespan and contribute to heterogeneity in risk of infectious diseases and response to vaccination. Sexual dimorphism is, in part, driven by sex hormones and has been demonstrated in both innate and adaptive immunity; testosterone has an immunosuppressive effect while estrogen is immunoenhancing. Thus, females tend to mount stronger immune responses, exhibit lower infection rates for a variety of pathogens, and demonstrate elevated responses to vaccination. However, the molecular mechanisms driving enhanced immunity in females are not well understood, and the degree to which exogenous sex hormones contribute to immune response is unknown. To dissect the role of female sex hormones in enhanced immunity and to broaden our understanding of sexual dimorphism in immunity and health, we propose to study the immune responses of adult transgender women (TW, individuals who identify as women but were assigned male at birth) undergoing gender-affirming hormone therapy (GAHT). This will provide a unique opportunity to understand the impact of sex hormones on the immune system generally, and more specifically, in response to the updated seasonal COVID-19 vaccines. No studies have examined interactions between COVID-19 vaccines and GAHT. We hypothesize that TW undergoing feminizing GAHT will develop enhanced immune responses that align more with their gender identity than their biological sex. Uptake of the 2023-24 seasonal COVID-19 vaccine is currently low in transgender people (12.5%), which is problematic since they are more likely to become severely ill, die, or incur COVID-related social harms (e.g., violence, job loss) if infected, however, 63% are open to it. Untangling the relationship between immune response and gender in TW may facilitate and improve evidence-based uptake of the seasonal COVID-19 vaccines in this population. Evidence from other fields (e.g., HIV) shows that TW are unlikely to use biomedical products (including vaccines) unless there exist biomedical and behavioral data specific to this population. However, to facilitate uptake and a sustained use In TW of the COVID-19 vaccines offered, we must understand not only their immunological response profile, but also their barriers, facilitators, and motivators to use. In Aim 1, humoral and cellular responses in adult TW (21-49 years) before and after immunization with the updated seasonal COVID-19 vaccine, when offered, will be compared to those elicited in clinically- and age-matched cisgender men and women with similar COVID-19 vaccine uptake and prior infections histories, and who are planning to receive the updated vaccine and be bled prior to immunization (baseline) followed by three bleeds 7-, 28- and 180-days post vaccination. In Aim 2, we will use the COM-B model and engage the TW in surveys, interviews, and in an intervention development work group before we develop a draft intervention (“OptimizeVax”) to facilitate updated seasonal COVID-19 vaccine uptake. Together, the aims comprise a critical first step towards determining if GAHT has immunoenhancing effects, and a foundation how to facilitate COVID-19 vaccines uptake by TW.
