Dottorato in ADVANCES IN INFECTIOUS DISEASES, MICROBIOLOGY, LEGAL
MEDICINE AND PUBLIC HEALTH SCIENCES

Titolo della tesi: Cellular immunity in immunocompromised individuals: vaccines, co-infections and new therapies

Abstract In this thesis, two research conducted on two different immunocompromised population, people living with HIV and solid organ transplant recipients, will be presented and discussed. The first part of my PhD happened during the COVID-19 Pandemic. During this period there was a need to answer questions about the effects of vaccination in immunocompromised populations, specifically describing the humoral and specifically T cell response to the mRNA-BNT162b vaccine. For this reason, part of this study discusses the results about humoral and cellular immune responses after one year since the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in SOT-Rs, with a focus on the qualitative characterization of T-cell response against the Omicron variant. Collectively, our data support the hypothesis that in SOT-Rs the administration of SARS-CoV-2 mRNA-based vaccine might elicit a weaker humoral and cellular immune response compared to HDs, suggesting that in SOT-Rs the third vaccine dose effect might wane during a 1-year observation period and perhaps booster doses should be considered. Moreover, in our study, the organ transplanted as well as the time elapsed since transplant affects vaccine immunogenicity after a third BNT162b2 dose in SOT-Rs, especially in antibody levels. However, T-cell-mediated response seems to be retained which is mainly important given the emergence of the Omicron sub lineages of SARS-CoV-2. The second part of this study describes the use of long-acting injectable (LA) therapy that, in addition to ensuring higher levels of adherence to prophylaxis and superior efficacy compared to oral prophylaxis, constitute a milestone in the development of strategies aimed at achieving the objective of “getting to zero”, a Public Health aim of States and International agencies and the current primary objective of the entire scientific and social community committed in the fight against HIV. In addition, the topic of HIV-CMV co-infection will be discussed. Starting from present data in literature, it is known that over 70-90% of PLWH are co-infected with CMV, which contributes to persistent immune activation. Our study discusses that, In PLWH, after 1 year from switch to CAB/RPV LA the percentage of senescent CD8+ T cells decrease. Although at T0 activated CD4+ T cells positively correlated with CMV-specific T cell responses, after 1 year this is no confirmed. Finally, in PLWH, CMV humoral and specific T-cells response were associated with senescent CD8+ T cells at 28 weeks from switch therapy. To date, the immunological mechanisms are not fully understood, and although it seems that changes in the immune response are due to the switch therapy, the role that CMV may have in driving these changes in the immune response needs to be better understood.