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

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.

Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation

Exposure of the adaptive immune system to a pathogen can result in the activation and expansion of T cells capable of recognizing not only the specific antigen but also different unrelated antigens, a process which is commonly referred to as heterologous immunity. While such cross-reactivity is favourable in amplifying protective immune responses to pathogens, induction of T cell-mediated heterologous immune responses to allo-antigens in the setting of solid organ transplantation can potentially lead to allograft rejection. In this review, we provide an overview of murine and human studies investigating the incidence and functional properties of virus-specific memory T cells cross-reacting with allo-antigens and discuss their potential relevance in the context of solid organ transplantation.

Immunological Features and Hypotheses: Do SARS-CoV and MERS-CoV-Reported Individuals have Immunity against SARS-CoV-2 Infection

COVID-19 spreads abnormally compared to its counterparts in the same family "beta-coronaviruses". Today, we count more than 130 million affected humans affected by the COVID-19. Therefore, the study of means of prevention and treatment is an urgent need. Interestingly, the novel virus (SARS-CoV-2) has some similarities with SARS-CoV and MERS-CoV. It is known that heterologous immunity is well recognized within species of the same family. The use of previously recognized effective antibodies for SARS and MERS virus may prevent the COVID-19 pandemic. The objective of this study is to compare between SARS-CoV, MERS-CoV, and SARS-CoV-2 genomic and proteomic identity/similarity and their cross-immunity as well as their immunological features in the context of COVID-19 diseases prevention and treatment methods.

Heterologous Immunity and Hepatitis C Virus: Impact on Natural Infection, Pathogenesis and Vaccine Design

Chronic infection with the hepatitis C virus (HCV) afflicts 1%–3% of the world’s population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain. Host immune responses play an important role in the outcome of infection with HCV. They can lead to viral clearance and a positive outcome, or progression and severity of the chronic disease. Studies of natural immunity to HCV in humans have resulted in many enigmas. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions, implicating the role of unknown factors and events. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T and B cells. This pool of memory T and B cells can cross-react against a new pathogen in an individual and thereby influence the outcome of the new infection. In our recent studies, we made the surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses, and that immunizing mice with a non-replicating, non-recombinant adenovirus (Ad) vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. We also extended this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive/heterologous immunity can a) accommodate the development of dual-pathogen vaccines, b) play an important role in the natural course of HCV infection, and c) provide a plausible answer to many unexplained questions regarding immunity to HCV.