Use of serological and molecular techniques to determine prior infection status and guide vaccine strategies in at-risk groups

Aims and objectives: Healthcare workers and recipients of haematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T-cells (CAR-T) are at increased risk from vaccine preventable diseases. My thesis incorporates four published papers presenting molecular and serological data, aimed at studying infection status and antibody responses in these groups to guide vaccine strategies.
Methods and Results: In Paper 1 and Paper 2, I investigated COVID-19 infection status. Paper 1 presented early findings from in-house molecular testing when capacity was limited, and Paper 2 explored healthcare worker serostatus. Seroprevalence data revealed approximately one quarter were infected during the first pandemic wave. Healthcare workers on the Acute Medical Unit and physio/occupational therapists were most likely to be seropositive. Antibody titre correlated positively with age, suggesting seroprevalence studies may underestimate infection status in younger populations.
Paper 3 and Paper 4 focussed on humoral immunity in HSCT/CAR-T recipients. In Paper 3, I applied a pseudoneutralisation assay to evaluate SARS-CoV-2 neutralising antibody responses following COVID-19 vaccination. Compared to healthcare workers, HSCT/CAR-T recipients had significantly poorer responses, particularly after one dose. Those who received viral vector vaccines were more likely to develop neutralising antibodies than messenger ribonucleic acid (mRNA) vaccinees. Older age, rituximab and prior HSCT were associated with lower titres. In Paper 4, I investigated binding antibody responses against a range of vaccine preventable diseases in autologous HSCT recipients who missed their re-vaccination schedule. This cohort had significant humoral defects, with the vast majority susceptible to pneumococcal disease and diphtheria. Following re-vaccination, increases in antibody titres were observed.
Conclusions: Improved awareness of factors associated with exposure among healthcare workers presents an opportunity to reduce risk through targeted interventions. Bespoke vaccination programmes post-HSCT/CAR-T are needed. Further exploration into the immunogenicity of different vaccine platforms would be valuable in this unique cohort.