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

https://doi.org/10.1016/j.jacig.2023.100091Get rights and content
Under a Creative Commons license
open access

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.

Key words

COVID-19
SARS-CoV-2
vaccine
ChAdOx1-nCoV-19
BNT162b2
immunodeficiency
antibodies
T cells
immunoglobulins
health care workers

Abbreviations used

CEFT
Peptides pool from human cytomegalovirus, Epstein-Barr virus, influenza A virus, and Clostridium tetani
COVID-19
Coronavirus disease 2019
CVID
Common variable immunodeficiency
HCW
Health care worker
HCW-nPI
HCW with no prior COVID-19 infection
HCW-PI
HCW with prior COVID-19 infection
IDP
Immunodeficient patient
IgGRx
Immunoglobulin replacement therapy
PV1
Post first vaccine dose
PV2
Post second vaccine dose
RBD
Receptor binding domain
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

Cited by (0)

The first 2 authors contributed equally to this article, and both should be considered first author. The last 2 authors contributed equally to this article, and both should be considered senior author.

Supported by the NIHR/UKRI (grant COV0170) Humoral Immune Correlates of COVID-19 (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.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.