Effect of Bacille Calmette-Guérin Vaccination on Immune Responses to SARS-CoV-2 and COVID-19 Vaccination

Overview

Journal Clin Transl Immunology

Date 2025 Jan 28

PMID 39872402

Authors

Nicole L Messina

Susie Germano

Amy W Chung

Carolien E van de Sandt

Natalie E Stevens

Lilith F Allen

Rhian Bonnici

Julio Croda

Claudio Counoupas

Branka Grubor-Bauk

Ebene R Haycroft

Katherine Kedzierska

Ellie McDonald

Rebecca McElroy

Mihai G Netea

Boris Novakovic

Kirsten P Perrett

Laure F Pittet

Ruth A Purcell

Kanta Subbarao

James A Triccas

David J Lynn

Nigel Curtis

Affiliations

Soon will be listed here.

Abstract

Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination. SARS-CoV-2-specific antibodies were measured using ELISA and multiplex bead array, whole blood cytokine responses to γ-irradiated SARS-CoV-2 (iSARS) stimulation were measured by multiplex bead array, and SARS-CoV-2-specific T-cell responses were measured by activation-induced marker and intracellular cytokine staining assays.

Results: After randomisation (mean 11 months) but prior to COVID-19 vaccination, the BCG group had lower cytokine responses to iSARS stimulation than the Control group. After two doses of ChAdOx1-S, differences in iSARS-induced cytokine responses between the BCG group and Control group were found for three cytokines (CTACK, TRAIL and VEGF). No differences were found between the groups after BNT162b2 vaccination. There were also no differences between the BCG and Control groups in COVID-19 vaccine-induced antigen-specific antibody responses, T-cell activation or T-cell cytokine production.

Conclusion: BCG vaccination induced a broad and persistent reduction in cytokine responses to SARS-CoV-2. Following COVID-19 vaccination, this effect was abrogated, and BCG vaccination did not influence adaptive immune responses to COVID-19 vaccine antigens.

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