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BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

ABSTRACT: The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.

SUBMITTER: Koti M

PROVIDER: S-EPMC7342862 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

Koti Madhuri M Morales Alvaro A Graham Charles H CH Siemens David Robert DR

Journal for immunotherapy of cancer 20200701 2

The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal m ...[more]

PMID: 32636240

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Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

Dataset Information

BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

Publications

BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

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