BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population

Authors

Najeeha Talat Iqbal, Aga Khan UniversityFollow
Kumail Ahmed, Aga Khan UniversityFollow
Tehniat Sattar, Aga Khan University
Fatima Aziz, Aga Khan UniversityFollow
Rabia Hussain, Aga Khan UniversityFollow

Document Type

Article

Department

Biological and Biomedical Sciences; Paediatrics and Child Health; Pathology and Laboratory Medicine

Abstract

Background: Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses.
Objective: To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections.
Study design: In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition.
Methods: BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay.
Results: Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG.
Conclusion: The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

Comments

Pagination is not provided by author/publisher.

Publication (Name of Journal)

PLOS ONE

DOI

10.1371/journal.pone.0302722

Recommended Citation

Iqbal, N., Ahmed, K., Sattar, T., Aziz, F., Hussain, R. (2024). BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population. PLOS ONE, 19(5).
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/1053