BCG and COVID-19
The BCG vaccine is a crucial tool for protecting babies and young children in high burden countries from TB, which killed 1.5 million people in 2019 and caused 10 million people to fall sick. Recent media reports indicating that BCG, the only licensed vaccine to protect again TB, may be protective against COVID-19 have led to new interest in this century-old vaccine. However, BCG’s ability to protect against COVID-19 infection or disease has not yet been tested in rigorous, prospective, randomized, controlled clinical trials. Such trials are now underway to study the effects of BCG in healthcare workers and others at high risk of COVID-19. Decisions on use of BCG to protect against COVID-19 should await these results and adequate supplies of BCG should be preserved to protect infants and children in high burden countries from TB.
For more information on this issue, please refer to the following resources:
- WHO Scientific Brief on Bacille Calmette-Guérin (BCG) vaccination and COVID-19
- Treatment Action Group Statement and Information Note on BCG Vaccine and COVID-19
- Bacille Calmette-Guérin (BCG) vaccine and the COVID-19 pandemic: responsible stewardship is needed, HS Schaaf et al., International Journal of Tuberculosis and Lung Disease
Resources about TB
and TB Vaccine R&D
- Meeting Report: 5th Global Forum on TB Vaccines, 21-24 February 2018, New Delhi, India, published open access in Tuberculosis (Dec 2018)
- TB Vaccines Pipeline Report is a report from Treatment Action Group (TAG) that reviews progress in the clinical development of TB vaccines. The report is updated annually.
- End TB Strategy from the World Health Organization’s Global TB Programme provides a 20-year strategy toward the goal of ending the TB epidemic, including research, development, and implementation of new tools.
- Global Plan to End TB 2018-2022 is a costed plan and roadmap for a concerted response to tuberculosis (TB) aligned with the United Nations (UN) Political Declaration on TB, including a strategic framework for TB vaccine R&D.
- WHO Preferred Product Characteristics for New Tuberculosis Vaccine presents WHO preferences for new tuberculosis vaccines, driven by the high medical need for contribution to the fight against TB, in alignment with the End TB strategy.
- Global Tuberculosis Report, published by the WHO, provides a comprehensive and up-to-date assessment of the TB epidemic, and of progress in prevention, diagnosis and treatment of the disease at global, regional and country levels. The report is updated annually.
- TB Vaccine Development Pathway, developed by IAVI and TBVI, is a tool that provides a structured development path and gating criteria for TB vaccine candidates. It also describes the different functions and capabilities required to advance a candidate TB vaccine to its next stage of development.
- Global Investments in Tuberculosis Research and Development: Past, Present, and Future is a policy paper developed by WHO in collaboration with civil society groups, academia, and product development partnerships to articulate the research and funding needs to end TB.
- TB Research Investments Provide Returns in Combating Both TB and COVID-19 is a policy brief published by Treatment Action Group (TAG) that explores the impact of COVID-19 on TB research and development (R&D), and how tools, concepts, capacity, and infrastructure established through years of public and donor investments in TB R&D have informed and jump-started COVID-19 research and responses.
- The impact of COVID-19 on the TB epidemic: a community perspective, provides the results of a civil society and affected community led survey to better understand how COVID-19 is impacting key stakeholder groups.
- BCG World Atlas is an interactive map that provides detailed information on current and past BCG vaccination policies and practices for over 180 countries.
Resources for Advocacy and Community Engagement
- The Urgent Need for New TB Vaccines is a fact sheet developed by WGNV that highlights the importance of new TB vaccines, and the strategy and funding needed to develop them.
- Vital Role for of Research for TB Elimination is a briefing document from TAG, WGNV and several other partners that provides information on TB R&D and its centrality to universal health coverage in preparation for the United National High Level Meeting on TB.
- Report on Tuberculosis Research Funding Trends, published annually by TAG, tracks how much public, private, philanthropic, and multilateral institutions spend on TB research and development (R&D) across six areas of research: basic science, diagnostics, drugs vaccines, operational research, and infrastructure/unspecified projects.
- Good Participatory Practice Guidelines for TB Vaccine Research, published by Aeras, is a user- friendly framework that defines specific standards and key elements needed for creating effective partnerships with stakeholders throughout the entire research process. Contact us if you are interested in obtaining copies of the GPP guidelines for TB vaccine research.
- Frequently Asked Questions on TB Vaccine Research, published by IAVI, is a fact sheet that provides information and answers to commonly asked questions about TB vaccine research.
- Myths and Facts about TB Vaccine Research, by IAVI, is a fact sheet that responds to some common misconceptions about vaccine research.
- Tuberculosis Vaccines and Clinical Trials, published by IAVI, provides information about TB, vaccines, and clinical trials in an illustrative and easy to understand booklet.
- Being Part of Tuberculosis Vaccine Clinical Trials is a speaking book published by Books of Hope in collaboration with Aeras, that provides potential clinical trial participants with information about tuberculosis and what is involved in participating in a clinical trial. The information is in both English and Afrikaans. Hard copies of the speaking book are available on request. Contact us if you are interested in obtaining copies of the speaking book.
Recent Scientific Publications
Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening. Huang H, Wang C, Rubelt F, Scriba TJ, Davis MM. Nat Biotechnol. 2020 Oct. doi: 10.1038/s41587-020-0505-4. Epub 2020 Apr 27.
Development of a novel T cell-oriented vaccine using CTL/Th-hybrid epitope long peptide and biodegradable microparticles, against an intracellular bacterium. Tanaka K, Enomoto N, Uehara M, Furuhashi K, Sakurai S, Yasui H, Karayama M, Hozumi H, Suzuki Y, Fujisawa T, Inui N, Nakamura Y, Nagata T, Suda T. Microbiol Immunol. 2020 Oct. doi: 10.1111/1348-0421.12836. Epub 2020 Oct 5.
BCG vaccination: An update on current Australian practices. Taylor JW, Curtis N, Denholm J. Aust J Gen Pract. 2020 Oct. doi: 10.31128/AJGP-06-20-5490.
Antituberculosis BCG vaccination: more reasons for varying innate and adaptive immune responses. Prentice S, Dockrell HM. J Clin Invest. 2020 Oct 1. doi: 10.1172/JCI141317.
Circadian rhythm influences induction of trained immunity by BCG vaccination. de Bree LCJ, Mourits VP, Koeken VA, Moorlag SJ, Janssen R, Folkman L, Barreca D, Krausgruber T, Fife-Gernedl V, Novakovic B, Arts RJ, Dijkstra H, Lemmers H, Bock C, Joosten LA, van Crevel R, Benn CS, Netea MG. J Clin Invest. 2020 Oct 1. doi: 10.1172/JCI133934.
BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner. Koeken VA, de Bree LCJ, Mourits VP, Moorlag SJ, Walk J, Cirovic B, Arts RJ, Jaeger M, Dijkstra H, Lemmers H, Joosten LA, Benn CS, van Crevel R, Netea MG. J Clin Invest. 2020 Oct 1. doi: 10.1172/JCI133935.
Prioritizing infants in a time of Bacille Calmette-Guerin vaccine shortage caused by premature expectations against COVID-19. Senoo Y, Suzuki Y, Takahashi K, Tsuda K, Tanimoto T. QJM. 2020 Oct 1. doi: 10.1093/qjmed/hcaa179.
An Overview of the Development of New Vaccines for Tuberculosis. Whitlow E, Mustafa AS, Hanif SNM. Vaccines (Basel). 2020 Oct 5. doi: 10.3390/vaccines8040586.
Targeting immunometabolism in host defence against Mycobacterium tuberculosis. Sheedy FJ, Divangahi M. Immunology. 2020 Oct 6. doi: 10.1111/imm.13276. Online ahead of print.
BCG vaccination of infants confers Mycobacterium tuberculosis strain-specific immune responses to leucocytes. Subbian S, Singh P, Kolloli A, Nemes E, Scriba T, Hanekom W, Kaplan G. Authorea. 2020 Oct 6. doi: 10.22541/au.160196958.83895007/v1
Potential impact of tuberculosis vaccines in China, South Africa, and India. Harris RC, Sumner T, Knight GM, Zhang H, White RG. Sci Transl Med. 2020 Oct 7. doi: 10.1126/scitranslmed.aax4607.
Evaluation of cytokines as a biomarker to distinguish active tuberculosis from latent tuberculosis infection: a diagnostic meta-analysis. Qiu B, Liu Q, Li Z, Song H, Xu D, Ji Y, Jiang Y, Tian D, Wang J. BMJ Open. 2020 Oct 7. doi: 10.1136/bmjopen-2020-039501.
The Systematic Review and Meta-Analysis on the Immunogenicity and Safety of the Tuberculosis Subunit Vaccines M72/AS01(E) and MVA85A. Ullah I, Bibi S, Ul Haq I, Safia, Ullah K, Ge L, Shi X, Bin M, Niu H, Tian J, Zhu B. Front Immunol. 2020 Oct 8. doi: 10.3389/fimmu.2020.01806. eCollection 2020.
The role of immunoinformatics in the development of T-cell peptide-based vaccines against Mycobacterium tuberculosis. Ortega-Tirado D, Arvizu-Flores AA, Velazquez C, Garibay-Escobar A. Expert Rev Vaccines. 2020 Oct 8. doi: 10.1080/14760584.2020.1825950. Online ahead of print.
BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case. Syggelou A, Spyridis N, Benetatou K, Kourkouni E, Kourlaba G, Tsagaraki M, Maritsi D, Eleftheriou I, Tsolia M. J Clin Med. 2020 Oct 8. doi: 10.3390/jcm9103224.
Editorial: Mycobacterial Glycolipids-Role in Immunomodulation and Targets for Vaccine Development. Källenius G, Nigou J, Cooper A, Correia-Neves M. Front Immunol. 2020 Oct 8. doi: 10.3389/fimmu.2020.603900. eCollection 2020.
Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines. Rozot V, Nemes E, Geldenhuys H, Musvosvi M, Toefy A, Rantangee F, Makhethe L, Erasmus M, Bilek N, Mabwe S, Finak G, Fulp W, Ginsberg AM, Hokey DA, Shey M, Gurunathan S, DiazGranados C, Bekker LG, Hatherill M, Scriba TJ; C-040-404 Study Team. Commun Biol. 2020 Oct 9. doi: 10.1038/s42003-020-01288-3.
Fast-acting γδ T-cell subpopulation and protective immunity against infections. Shen L, Huang D, Qaqish A, Frencher J, Yang R, Shen H, Chen ZW. Immunol Rev. 2020 Oct 10. doi: 10.1111/imr.12927. Online ahead of print.
When it’s good to have MAITs. Souter MN, McCluskey J, Corbett AJ. Immunol Cell Biol. 2020 Oct 11. doi: 10.1111/imcb.12402. Online ahead of print.
Mycobacterium tuberculosis extracellular vesicles: exploitation for vaccine technology and diagnostic methods. Mohammadzadeh R, Ghazvini K, Farsiani H, Soleimanpour S. Crit Rev Microbiol. 2020 Oct 12. doi: 10.1080/1040841X.2020.1830749. Online ahead of print.
Vaccine strategies for the Mtb/HIV copandemic. Sharan R, Kaushal D. NPJ Vaccines. 2020 Oct 13. doi: 10.1038/s41541-020-00245-9. eCollection 2020.
Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Antonakos N, Kotsaki A, Domínguez-Andrés J, Kyriazopoulou E, Gkavogianni T, Adami ME, Damoraki G, Koufargyris P, Karageorgos A, Bolanou A, Koenen H, van Crevel R, Droggiti DI, Renieris G, Papadopoulos A, Netea MG. Cell. 2020 Oct 15. doi: 10.1016/j.cell.2020.08.051. Epub 2020 Sep 1.
Immunization with Mycobacterium tuberculosis-Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guerin Vaccination and Improves Protection in Mice. Aagaard C, Knudsen NPH, Sohn I, Izzo AA, Kim H, Kristiansen EH, Lindenstrøm T, Agger EM, Rasmussen M, Shin SJ, Rosenkrands I, Andersen P, Mortensen R. J Immunol. 2020 Oct 15. doi: 10.4049/jimmunol.2000563. Epub 2020 Sep 4.
Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis. Li Z, Bavaro T, Tengattini S, Bernardini R, Mattei M, Annunziata F, Cole RB, Zheng C, Sollogoub M, Tamborini L, Terreni M, Zhang Y. Eur J Med Chem. 2020 Oct 15. doi: 10.1016/j.ejmech.2020.112578. Epub 2020 Jul 15.
Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection. Duffy D, Nemes E, Llibre A, Rouilly V, Musvosvi M, Smith N, Filander E, Africa H, Mabwe S, Jaxa L, Charbit B, Mulenga H; Milieu Intérieur Consortium, Tameris M, Walzl G, Malherbe S, Thomas S, Hatherill M, Bilek N, Scriba TJ, Albert ML. Clin Infect Dis. 2020 Oct 16. doi: 10.1093/cid/ciaa1562. Online ahead of print.
A natural polymorphism of Mycobacterium tuberculosis in the esxH gene disrupts immunodomination by the TB10.4-specific CD8 T cell response. Sutiwisesak R, Hicks ND, Boyce S, Murphy KC, Papavinasasundaram K, Carpenter SM, Boucau J, Joshi N, Le Gall S, Fortune SM, Sassetti CM, Behar SM. PLoS Pathog. 2020 Oct 19. doi: 10.1371/journal.ppat.1009000. eCollection 2020 Oct.
Efficient 5-OP-RU-induced enrichment of Mucosal-associated invariant T cells in the murine lung does not enhance control of aerosol Mycobacterium tuberculosis infection. Vorkas CK, Levy O, Skular M, Li K, Aubé J, Glickman MS. Infect Immun. 2020 Oct 19. doi: 10.1128/IAI.00524-20. Online ahead of print.
Mycobacterium tuberculosis curli pili (MTP) is associated with significant host metabolic pathways in an A549 epithelial cell infection model and contributes to the pathogenicity of Mycobacterium tuberculosis. Reedoy KS, Loots DT, Beukes D, Reenen MV, Pillay B, Pillay M. Metabolomics. 2020 Oct 21;16(11):116. doi: 10.1007/s11306-020-01736-5.
BCG-Prime and boost with Esx-5 secretion system deletion mutant leads to better protection against clinical strains of Mycobacterium tuberculosis. Tiwari S, Dutt TS, Chen B, Chen M, Kim J, Dai AZ, Lukose R, Shanley C, Fox A, Karger BR, Porcelli SA, Chan J, Podell BK, Obregon-Henao A, Orme IM, Jacobs WR Jr, Henao-Tamayo M. Vaccine. 2020 Oct 21;38(45):7156-7165. doi: 10.1016/j.vaccine.2020.08.004. Epub 2020 Sep 23.
CD8 T Cells Show Protection against Highly Pathogenic Simian Immunodeficiency Virus (SIV) after Vaccination with SIV Gene-Expressing BCG Prime and Vaccinia Virus/Sendai Virus Vector Boosts. Kato S, Shida H, Okamura T, Zhang X, Miura T, Mukai T, Inoue M, Shu T, Naruse TK, Kimura A, Yasutomi Y, Matsuo K. J Virol. 2020 Oct 21. doi: 10.1128/JVI.01718-20. Online ahead of print.
Fusion of Dendritic Cells Activating Rv2299c Protein Enhances the Protective Immunity of Ag85B-ESAT6 Vaccine Candidate against Tuberculosis. Back YW, Bae HS, Choi HG, Binh DT, Son YJ, Choi S, Kim HJ. Pathogens. 2020 Oct 22. doi: 10.3390/pathogens9110865.
Vaccination with Intradermal Bacillus Calmette-Guerin Provides Robust Protection against Extrapulmonary Tuberculosis but Not Pulmonary Infection in Cynomolgus Macaques. Tsujimura Y, Shiogama Y, Soma S, Okamura T, Takano J, Urano E, Murakata Y, Kawano A, Yamakawa N, Asaka MN, Matsuo K, Yasutomi Y. J Immunol. 2020 Oct 23. Online ahead of print.
Evaluation of patients with primary immunodeficiency associated with Bacille Calmette-Guerin (BCG)-vaccine-derived complications. Sohani M, Habibi S, Delavari S, Shahkarami S, Yazdani R, Shirmast P, Nazari F, Shad TM, Mamishi S, Azizi G, Anka AU, Hassanpour G, Kalantari A, Shariat M, Shafiei A, Abolhassani H, Aghamohammadi A. Allergol Immunopathol (Madr). 2020 Oct 25. doi: 10.1016/j.aller.2020.04.004.
Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis. Zhao SY, Li N, Luo WY, Zhang NN, Zhou RY, Li CY, Wang J. Chem Commun (Camb). 2020 Oct 26. doi: 10.1039/d0cc05573e. Online ahead of print.
DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial. Munseri P, Said J, Amour M, Magohe A, Matee M, Rees CA, Mackenzie T, Tvaroha S, Bailey-Kellogg C, Maro I, Wieland-Alter W, Adams LV, Horsburgh CR, Nakamura K, Arbeit RD, Pallangyo K, von Reyn CF. Vaccine. 2020 Oct 27. doi: 10.1016/j.vaccine.2020.09.055. Epub 2020 Sep 29.
Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis. Plumlee CR, Duffy FJ, Gern BH, Delahaye JL, Cohen SB, Stoltzfus CR, Rustad TR, Hansen SG, Axthelm MK, Picker LJ, Aitchison JD, Sherman DR, Ganusov VV, Gerner MY, Zak DE, Urdahl KB. Cell Host Microbe. 2020 Oct 27. doi: 10.1016/j.chom.2020.10.003. Online ahead of print.
M. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity. Khan N, Downey J, Sanz J, Kaufmann E, Blankenhaus B, Pacis A, Pernet E, Ahmed E, Cardoso S, Nijnik A, Mazer B, Sassetti C, Behr MA, Soares MP, Barreiro LB, Divangahi M. Cell. 2020 Oct 29. coi: 10.1016/j.cell.2020.09.062
Airway delivery of both a BCG prime and adenoviral boost drives CD4 and CD8 T cells into the lung tissue parenchyma. Kaveh DA, Garcia-Pelayo MC, Bull NC, Sanchez-Cordon PJ, Spiropoulos J, Hogarth PJ. Sci Rep. 2020 Oct 30. doi: 10.1038/s41598-020-75734-x.
New tuberculosis vaccines: advances in clinical development and modelling. Weerasuriya CK, Clark RA, White RG, Harris RC. J Intern Med. 2020 Oct 31. doi: 10.1111/joim.13197. Online ahead of print.