Touizer, Emma; (2024) B cell and antibody responses to SARS-CoV-2 in people living with HIV. Doctoral thesis (Ph.D), UCL (University College London).

Text Touizer_10191692_thesis_sig_removed.pdf Access restricted to UCL open access staff until 1 June 2025. Download (24MB)

Abstract

People living with HIV (PLWH) have ongoing immune dysfunction despite successful antiretroviral treatment. In PLWH, B cells and antibodies phenotype, function, and development are disrupted. However, there is still no clear investigation into how this overall B cell disruption in PLWH leads to the worse serological outcomes observed in vaccination. This thesis aims to characterise the humoral and cellular response made by PLWH against a novel pathogen, SARS-CoV-2, following infection or vaccination. Participants were either recruited following SARS-CoV-2 infection (47 PLWH and 35 HIV-negative controls) or following 1, 2 or 3 doses of SARS-CoV-2 vaccines (111 PLWH and 64 HIV-negative controls). SARS-CoV-2 infection provided a sufficient stimulus so that PLWH’s binding and neutralising antibody titres were comparable to HIV-negative controls. However, following SARS-CoV-2 vaccination, PLWH’s serological output was lower compared to HIV-negative controls after each vaccine dose, regardless of previous SARS-CoV-2 infection. After the 1st vaccine dose, the neutralisation response of PLWH was delayed compared to HIV-negative controls. This delay was associated with lower frequencies of spike-specific memory B cells (MBC) and perturbed MBCs phenotype characterised by higher levels of atypical MBCs. After the 3rd vaccine dose, PLWH still had lower titres and breadth of neutralising antibodies, alongside perturbed MBCs phenotype compared to HIV- negative controls despite having similar frequencies of spike-specific MBCs. To answer if this MBC defect leads to improper recall responses in PLWH and thus inadequate affinity maturation, 10 PLWH and 10 HIV-negative individuals were chosen to sequence their bulk and antigen-specific BCR repertoire after each dose of SARS- CoV-2 vaccination. This showed that at the clonal level, PLWH’s antibody repertoire was less diverse and skewed towards aberrant somatic hypermutation. Altogether, this thesis showed that despite adequate antigenic stimulation, PLWH struggle to overcome their initial MBCs defect and thus are less able to make a successful serological response.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item