Differential T-cell and Antibody Responses induced by mRNA versus adenoviral vectored COVID-19 vaccines in Patients with Immunodeficiencies

Background: Immunodeficient patients (IDPs) are at higher risk of contracting severe COVID-19 disease. Targeted vaccination strategies have been implemented to enhance vaccine-induced protection. In this population however, clinical effectiveness is variable and duration of protection unknown.

Objective: To understand the cellular and humoral immune responses to mRNA and adenoviral vectored COVID-19 vaccines in patients with immunodeficiency.

Methods: Immune responses to SARS-COV-2 spike were assessed after two doses of homologous ChAdOx1-nCoV-19 or BNT162b2 vaccines in 112 infection-naïve IDPs and 131 healthy health care workers (HCWs) as controls. Predictors of vaccine responsiveness were investigated.

Results: Immune responses to vaccination were low, and viral neutralisation by antibody not detected despite high titre binding responses in many IDPs. In those responding, the frequency of specific T-cell responses in IDPs was similar to controls whilst antibody responses were lower. Sustained vaccine specific differences were identified: T-cell responses were greater in ChAdOx1-nCoV-19 compared with BNT162b2 immunised IDPs and antibody binding and neutralisation was greater in all cohorts immunised with BNT162b2. The positive correlation between T-cell and antibody responses was weak and increased with subsequent vaccination.

Conclusion: Immunodeficient patients have impaired immune responses to mRNA and viral vector COVID-19 vaccines that appear influenced by vaccine formulation. Understanding the relative roles of T-cell and antibody mediated protection and potential of heterologous prime and boost immunization protocols is needed to optimise the vaccination approach in these high-risk groups.