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.
- BCG World Atlas is an interactive map that provides detailed information on current and past BCG vaccination policies and practices for over 180 countries.
- 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 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.
- 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.
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
Computational approaches in epitope design using DNA binding proteins as vaccine candidate in Mycobacterium tuberculosis. Sunita, Singhvi N, Singh Y, Shukla P. Infect Genet Evol. 2020 Sept. doi: 10.1016/j.meegid.2020.104357. Epub 2020 May 11.
BCG vaccination strategy implemented to reduce the impact of COVID-19: Hype or Hope? Rajarshi K, Chatterjee A, Ray S. Med Drug Discov. 2020 Sept. doi: 10.1016/j.medidd.2020.100049. Epub 2020 May 26.
New insights into the evasion of host innate immunity by Mycobacterium tuberculosis. Chai Q, Wang L, Liu CH, Ge B. Cell Mol Immunol. 2020 Sept. doi: 10.1038/s41423-020-0502-z. Epub 2020 Jul 29.
Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain. Kim A, Park KJ, Kim YS, Cho SN, Dockrell HM, Hur YG. Yonsei Med J. 2020 Sept. doi: 10.3349/ymj.2020.61.9.789.
Methylation in Mycobacterium-host interaction and implications for novel control measures. Asaad M, Abo-Kadoum MA, Nzungize L, Uae M, Nzaou SAE, Xie J. Infect Genet Evol. 2020 Sept. doi: 10.1016/j.meegid.2020.104350. Epub 2020 May 4.
IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants. Bartsch YC, Eschweiler S, Leliavski A, Lunding HB, Wagt S, Petry J, Lilienthal GM, Rahmöller J, de Haan N, Hölscher A, Erapaneedi R, Giannou AD, Aly L, Sato R, de Neef LA, Winkler A, Braumann D, Hobusch J, Kuhnigk K, Krémer V, Steinhaus M, Blanchard V, Gemoll T, Habermann JK, Collin M, Salinas G, Manz RA, Fukuyama H, Korn T, Waisman A, Yogev N, Huber S, Rabe B, Rose-John S, Busch H, Berberich-Siebelt F, Hölscher C, Wuhrer M, Ehlers M. J Allergy Clin Immunol. 2020 Sept. doi: 10.1016/j.jaci.2020.04.059. Epub 2020 May 21.
BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge. Suresh P, Biswas L, Prasad V, Kumar A, Sivadas S, Khan S, Biswas R. Am J Trop Med Hyg. 2020 Sept. doi: 10.4269/ajtmh.19-0853.
Identification of immunogenic T-cell peptides of Mycobacterium tuberculosis PE_PGRS33 protein. Ortega-Tirado D, Niño-Padilla EI, Arvizu-Flores AA, Velazquez C, Espitia C, Serrano CJ, Enciso-Moreno JA, Sumoza-Toledo A, Garibay-Escobar A. Mol Immunol. 2020 Sept. doi: 10.1016/j.molimm.2020.06.026. Epub 2020 Jul 10.
The effect of BCG vaccination on alveolar macrophages obtained from induced sputum from healthy volunteers. Koeken VACM, van der Pasch ES, Leijte GP, Mourits VP, de Bree LCJ, Moorlag SJCFM, Budnick I, Idh N, Lerm M, Kox M, van Laarhoven A, Netea MG, van Crevel R. Cytokine. 2020 Sept. doi: 10.1016/j.cyto.2020.155135. Epub 2020 Jun 10.
Immunization with Mycobacterium tuberculosis-Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guérin 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 Sept 4. doi: 10.4049/jimmunol.2000563. Online ahead of print.
COVID-19 death and BCG vaccination programs worldwide. Jirjees FJ, Dallal Bashi YH, Al-Obaidi HJ. Tuberc Respir Dis (Seoul). 2020 Sep 4. doi: 10.4046/trd.2020.0063. Online ahead of print.
Differential Immunogenicity and Protective Efficacy Elicited by MTO- and DMT-Adjuvanted CMFO Subunit Vaccines against Mycobacterium tuberculosis Infection. Ullah N, Hao L, Wu Y, Zhang Y, Lei Q, Banga Ndzouboukou JL, Lin X, Fan X. J Immunol Res. 2020 Sep 4. doi: 10.1155/2020/2083793.
Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine. Mahmood MS, Bin-T-Abid D, Irshad S, Batool H. Int J Pept Res Ther. 2020 Sep 4:1-18. doi: 10.1007/s10989-020-10111-w. Online ahead of print.
Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial. Watt J, Liu J. Pharmaceutics. 2020 Sep 6. doi: 10.3390/pharmaceutics12090848.
mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection. Xu S, Yang K, Li R, Zhang L. Int J Mol Sci. 2020 Sep 9. doi: 10.3390/ijms21186582.
Integrated transcriptomic and quantitative proteomic analysis identifies potential RNA sensors that respond to the Ag85A DNA vaccine. Zhai J, Gao W, Zhao L, Lu C. Microb Pathog. 2020 Sep 10. doi: 10.1016/j.micpath.2020.104487. Online ahead of print.
The impact of human single nucleotide polymorphisms on Bacillus Calmette-Guérin responses. Messina NL, Netea MG, Curtis N. Vaccine. 2020 Sep 11. doi: 10.1016/j.vaccine.2020.07.032. Epub 2020 Aug 18.
Recent progress in the design of DNA vaccines against tuberculosis. Sefidi-Heris Y, Jahangiri A, Mokhtarzadeh A, Shahbazi MA, Khalili S, Baradaran B, Mosafer J, Baghbanzadeh A, Hejazi M, Hashemzaei M, Hamblin MR, Santos HA. Drug Discov Today. 2020 Sep 11. doi: 10.1016/j.drudis.2020.09.005. Online ahead of print.
Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models. Ramos, L, Lunney, JK, Gonzalez-Juarrero, M. Dis Model Mech. 2020 Sep 15. doi: 10.1242/dmm.045740.
Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development. Pasco ST, Anguita J. Cells. 2020 Sep 16. doi: 10.3390/cells9092109.
A structured Markov chain model to investigate the effects of pre-exposure vaccines in tuberculosis control. Fernández-Peralta R, Gómez-Corral A. J Theor Biol. 2020 Sep 16. doi: 10.1016/j.jtbi.2020.110490. Online ahead of print.
Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark. Madsen AMR, Schaltz-Buchholzer F, Benfield T, Bjerregaard-Andersen M, Dalgaard LS, Dam C, Ditlev SB, Faizi G, Johansen IS, Kofoed PE, Kristensen GS, Loekkegaard ECL, Mogensen CB, Mohamed L, Ostenfeld A, Oedegaard ES, Soerensen MK, Wejse C, Jensen AKG, Nielsen S, Krause TG, Netea MG, Aaby P, Benn CS. Trials. 2020 Sep 17. doi: 10.1186/s13063-020-04714-3.
A multiple T cell epitope comprising DNA vaccine boosts the protective efficacy of Bacillus Calmette-Guérin (BCG) against Mycobacterium tuberculosis. Maurya SK, Aqdas M, Das DK, Singh S, Nadeem S, Kaur G, Agrewala JN. BMC Infect Dis. 2020 Sep 17. doi: 10.1186/s12879-020-05372-1.
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 Sep 18. doi: 10.1080/14760584.2020.1825950. Online ahead of print.
Luteolin-mediated Kv1.3 K+ channel inhibition augments BCG vaccine efficacy against tuberculosis by promoting central memory T cell responses in mice. Singh DK, Dwivedi VP, Singh SP, Kumari A, Sharma SK, Ranganathan A, Kaer LV, Das G. PLoS Pathog. 2020 Sep 21. doi: 10.1371/journal.ppat.1008887. Online ahead of print.
Antituberculosis BCG vaccination: more reasons for varying innate and adaptive immune responses.Prentice S, Dockrell HM. J Clin Invest. 2020 Sep 21. doi: 10.1172/JCI141317. Online ahead of print.
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 Sep 21. doi: 10.1172/JCI133934. Online ahead of print.
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 Sep 21. doi: 10.1172/JCI133935. Online ahead of print.
The effect of Bacillus Calmette-Guérin (BCG) vaccination in preventing severe infectious respiratory diseases other than TB: Implications for the COVID-19 pandemic.Yitbarek K, Abraham G, Girma T, Tilahun T, Woldie M. Vaccine. 2020 Sep 22. doi: 10.1016/j.vaccine.2020.08.018. Epub 2020 Aug 10.
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 Sep 22. doi: 10.1016/j.vaccine.2020.08.004. Online ahead of print.
Optimisation of Mycobacterium bovis BCG Fermentation and Storage Survival. Pascoe J, Hendon-Dunn CL, Birch CPD, Williams GA, Chambers MA, Bacon J. Pharmaceutics. 2020 Sep 22. doi: 10.3390/pharmaceutics12090900.
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 Sep 28. doi: 10.1016/j.vaccine.2020.09.055. Online ahead of print.
Identification of autophagy inhibiting factors of Mycobacterium tuberculosis by high throughput loss of function screening. Strong EJ, Jurcic Smith KL, Saini NK, Ng TW, Porcelli SA, Lee S. Infect Immun. 2020 Sep 28. doi: 10.1128/IAI.00269-20. Online ahead of print.
Airway Macrophages Mediate Mucosal Vaccine-Induced Trained Innate Immunity against Mycobacterium tuberculosis in Early Stages of Infection.D’Agostino MR, Lai R, Afkhami S, Khera A, Yao Y, Vaseghi-Shanjani M, Zganiacz A, Jeyanathan M, Xing Z. J Immunol. 2020 Sep 30. doi: 10.4049/jimmunol.2000532. Online ahead of print.