Hypothetical Immunological and Immunogenetic Model of Heterogenous Effects of BCG Vaccination in SARS-CoV-2 Infections: BCG-induced Trained and Heterologous Immunity

Dženan Kovačić; Andrej A. Gajić; Dado Latinović; Adna Softić

doi:10.20883/medical.e551

Authors

Dženan Kovačić International Burch University, Faculty of Engineering and Natural Sciences, Department of Genetics and Bioengineering, Sarajevo, Bosnia and Herzegovina; Sharklab ADRIA: Center for marine and frewater biology, Triq il-Kappella Tal-Lunzjata, In-Naxxar, Malta https://orcid.org/0000-0003-3218-5073
Andrej A. Gajić Shark Tales, Funded by the National Geographic Society, Washington, D.C., USA; Sharklab ADRIA: Center for marine and frewater biology, Triq il-Kappella Tal-Lunzjata, In-Naxxar, Malta https://orcid.org/0000-0001-5138-9368
Dado Latinović International Burch University, Faculty of Engineering and Natural Sciences, Department of Genetics and Bioengineering, Sarajevo, Bosnia and Herzegovina
Adna Softić International Burch University, Faculty of Engineering and Natural Sciences, Department of Genetics and Bioengineering, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-4405-2916

DOI:

https://doi.org/10.20883/medical.e551

Keywords:

immunogenetics, immunology, trained immunity, heterologous immunity, BCG trained immunity, TLR signalling, COVID-19 and BCG

Abstract

Though SARS-CoV-2 infections are yet to be completely characterised in a host-pathogen interaction context, some of the mechanisms governing the interaction between the novel betacoronavirus and the human host, have been brought to light in satisfactory detail. Among the emerging evidence, postulates regarding potential benefits of innate immune memory and heterologous immunity have been put under discussion. Innate immune memory entails epigenetic reprogramming of innate immune cells caused by vaccination or infections, whereas heterologous immunity denotes cross-reactivity of T cells with unrelated epitopes and bystander CD8+ activation. Familiarization of the host immune system with a certain pathogen, educates monocytes, macrophages and other innate cells into phenotypes competent for combating unrelated pathogens. Indeed, the resolution at which non-specific innate immune memory occurs, is predominant at the level of enhanced cytokine secretion as a result of epigenetic alterations. One vaccine whose non-specific effects have been documented and harnessed in treating infections, cancer and autoimmunity, is the Bacillus Calmette–Guérin (BCG) vaccine currently used for immunization against pulmonary tuberculosis (TB). The BCG vaccine induces a diverse cytokine secretion profile in immunized subjects, which in turn may stimulate epigenetic changes mediated by immunoreceptor signalling. Herein, we provide a concise summarization of previous findings regarding the effects of the BCG vaccine on innate immune memory and heterologous immunity, supplemented with clinical evidence of the non-specific effects of this vaccine on non-mycobacterial infections, cancer and autoimmunity. This interpretative synthesis aims at providing a plausible immunological and immunogenetic model by which BCG vaccination may, in fact, be beneficial for the current efforts in combating COVID-19.

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