The stark disparities in health outcomes revealed during the COVID-19 pandemic have highlighted an urgent need to understand the biological consequences of social inequality. This thesis explores the overall hypothesis that many of the health outcomes caused by social inequality are due to alterations within the immune system; specifically, it investigates how socioeconomic status (SES), homelessness, and psychosocial adversity shape trajectories of immune ageing and impact on vaccine responsiveness using two linked human cohorts: Assessing Effects of SES-Associated Psychosocial Stress on Vaccine-Induced Immunity to SARS-CoV-2 (AESS-Vax, n=164) and Premature Ageing in long-Term Homeless Adults (PATH, n=59). Participants were stratified by SES and housing status, and provided detailed sociodemographic, clinical, and psychosocial data alongside biological samples. Immune parameters assessed included SARS-CoV-2 vaccine-induced humoral and cellular immunity, multiplex cytokine profiling, and spectral cytometry-based immunophenotyping of lymphocyte subsets.

In an immune proteome screen of serum samples from this cohort, eight cytokines were found to be elevated in homeless compared to housed individuals. Differences were also observed by SES, though of lesser magnitude. Notably, the differences associated with homelessness persisted after adjusting for age, sex, smoking history, and alcohol consumpƟon. These cytokine profiles are consistent with observaƟons of the immune profile seen in "inflammageing", highlighting homelessness as a particularly strong immunological stressor. Furthermore, high-dimensional immunophenotyping revealed that participants from low SES backgrounds had reduced frequencies of naive CD4+ and CD8+ T cells...

P.58 Data collection for the PATH study was conducted through structured, face-toface interviews carried out by trained researchers. Interviews were conducted in private seƫngs within the hostels and included a combination of standardised and adapted instruments. The survey captured self-reported sociodemographic information (including age, gender, biological sex at birth, highest level of education completed, occupational history, history of incarceration), physical and mental health status, and current medication use. Participants were also asked about their use of alcohol, tobacco, and other drugs... 

P.73 Table 2.6 Summary of Demographic and Health Information Collected in the AESS-Vax Study includes: Smoking Status and History; Alcohol Consumption; Drug Use...