Differential T-cell and antibody responses induced by mRNA versus adenoviral vectored COVID-19 vaccines in patients with immunodeficiencies

Aguinam, E. T. et al. (2023) Differential T-cell and antibody responses induced by mRNA versus adenoviral vectored COVID-19 vaccines in patients with immunodeficiencies. Journal of Allergy and Clinical Immunology: Global, 2(2), 100091. (doi: 10.1016/j.jacig.2023.100091) (PMID:37038555) (PMCID:PMC10015741)

Abstract

Background Immunodeficient patients (IDPs) are at higher risk of contracting severe coronavirus disease 2019 (COVID-19). Targeted vaccination strategies have been implemented to enhance vaccine-induced protection. In this population, however, clinical effectiveness is variable and the duration of protection unknown. Objective We sought to better understand the cellular and humoral immune responses to mRNA and adenoviral vectored COVID-19 vaccines in patients with immunodeficiency. Methods Immune responses to severe acute respiratory syndrome coronavirus 2 spike were assessed after 2 doses of homologous ChAdOx1-nCoV-19 or BNT162b2 vaccines in 112 infection-naive IDPs and 131 healthy health care workers as controls. Predictors of vaccine responsiveness were investigated. Results Immune responses to vaccination were low, and virus neutralization by antibody was not detected despite high titer binding responses in many IDPs. In those exhibiting response, the frequency of specific T-cell responses in IDPs was similar to controls, while antibody responses were lower. Sustained vaccine specific differences were identified: T-cell responses were greater in ChAdOx1-nCoV-19– compared to BNT162b2-immunized IDPs, and antibody binding and neutralization were greater in all cohorts immunized 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 to be influenced by vaccine formulation. Understanding the relative roles of T-cell– and antibody-mediated protection as well as the potential of heterologous prime and boost immunization protocols is needed to optimize the vaccination approach in these high-risk groups.

• Item Type: Articles
• Additional Information: Supported by the NIHR/UKRI (grant COV0170) Humoral Immune Correlates of COVID19 (HICC), the NIHR/UK-HSA (MR/W02067X/1) SIREN study, the Royal Papworth Hospital NHS Foundation Trust Charity, and the Cambridge Commonwealth, European & International Trust (Cambridge Trust) in association with Cambridge–Africa.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cantoni, Dr Diego
• Authors: Aguinam, E. T., Nadesalingam, A., Chan, A., Smith, P., Paloniemi, M., Cantoni, D., Gronlund, J., Gronlund, H., Carnell, G. W., Castillo-Olivares, J., Temperton, N., Blacklaws, B., Heeney, J. L., and Baxendale, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Allergy and Clinical Immunology: Global
• Publisher: Elsevier
• ISSN: 2772-8293
• Copyright Holders: Copyright: © 2023 The Author(s)
• First Published: First published in Journal of Allergy and Clinical Immunology: Global 2(2): 100091
• Publisher Policy: Reproduced under a Creative Commons licence