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
New tuberculosis vaccines: advances in clinical development and modelling. Weerasuriya CK, Clark RA, White RG, Harris RC. J Intern Med. 2020 Dec. doi: 10.1111/joim.13197.
Is mapping the BCG vaccine-induced immune responses the key to improving the efficacy against tuberculosis? Kuan R, Muskat K, Peters B, Lindestam Arlehamn CS. J Intern Med. 2020 Dec. doi: 10.1111/joim.13191. Epub 2020 Nov 19.
Emerging patterns of regulatory T cell function in tuberculosis. Ahmed A, Vyakarnam A.Clin Exp Immunol. 2020 Dec. doi: 10.1111/cei.13488. Epub 2020 Sep 6.
Analysis of the Efficiency of Different Antituberculous Drugs and Approaches to Treat BCG-Induced Granulomatosis in Mice and Abundance and Localization of Mycobacterium tuberculosis in the Liver. Sinyavskaya AM, Shkurupy VA, Troitskii AV, Kovner AM. Bull Exp Biol Med. 2020 Dec. doi: 10.1007/s10517-020-05041-y. Epub 2020 Dec 3.
DNA Based Vaccines against Mycobacterium Tuberculosis: Recent Progress in Vaccine Development and Delivery System. Mobed A. Iran J Immunol. 2020 Dec. doi: 10.22034/iji.2020.87480.1806.
Paradigm shift in efforts to end TB by 2025. Sachdeva KS, Parmar M, Rao R, Chauhan S, Shah V, Pirabu R, Balasubramaniam D, Vadera B, Anand S, Mathew M, Solanki H, Sundar VV. Indian J Tuberc. 2020 Dec. Epub 2020 Nov 10.
Good old BCG – what a century-old vaccine can contribute to modern medicine. Locht C, Lerm M. J Intern Med. 2020 Dec. doi: 10.1111/joim.13195.
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 Dec. doi: 10.1016/j.micpath.2020.104487. Epub 2020 Sep 10.
BCG scarring and improved child survival: a combined analysis of studies of BCG scarring. Benn CS, Roth A, Garly ML, Fisker AB, Schaltz-Buchholzer F, Timmermann A, Berendsen M, Aaby P. J Intern Med. 2020 Dec. doi: 10.1111/joim.13084. Epub 2020 May 25.
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 Dec 1. doi: 10.4049/jimmunol.2000386. Epub 2020 Oct 23.
Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity. Bai C, Zhou L, Tang J, He J, Han J, Niu H, Zhu B. Vaccines (Basel). 2020 Dec 1. doi: 10.3390/vaccines8040715.
Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity.Bai C, Zhou L, Tang J, He J, Han J, Niu H, Zhu B. Vaccines (Basel). 2020 Dec 1. doi: 10.3390/vaccines8040715.
Key recent advances in TB vaccine development and understanding of protective immune responses against Mycobacterium tuberculosis.Scriba TJ, Netea MG, Ginsberg AM. Semin Immunol. 2020 Dec 2. doi: 10.1016/j.smim.2020.101431. Online ahead of print.
Development of a formulation platform for a spray-dried, inhalable tuberculosis vaccine candidate.Gomez M, McCollum J, Wang H, Ordoubadi M, Jar C, Carrigy NB, Barona D, Tetreau I, Archer M, Gerhardt A, Press C, Fox CB, Kramer RM, Vehring R.Int J Pharm. 2020 Dec 2. doi: 10.1016/j.ijpharm.2020.120121. Online ahead of print.
Development of a formulation platform for a spray-dried, inhalable tuberculosis vaccine candidate. Gomez M, McCollum J, Wang H, Ordoubadi M, Jar C, Carrigy NB, Barona D, Tetreau I, Archer M, Gerhardt A, Press C, Fox CB, Kramer RM, Vehring R. Int J Pharm. 2020 Dec 2. doi: 10.1016/j.ijpharm.2020.120121. Online ahead of print.
NOD2/RIG-I Activating Inarigivir Adjuvant Enhances the Efficacy of BCG Vaccine Against Tuberculosis in Mice. Khan A, Singh VK, Mishra A, Soudani E, Bakhru P, Singh CR, Zhang D, Canaday DH, Sheri A, Padmanabhan S, Challa S, Iyer RP, Jagannath C. Front Immunol. 2020 Dec 7. doi: 10.3389/fimmu.2020.592333. eCollection 2020.
The TB vaccine development pathway – An innovative approach to accelerating global TB vaccine development. Roordink D, Williams A, Fritzell B, Laddy DJ, Gerdil E, Graffin AM, Tait D, van der Pol L, van den Brink I, Holleman M, Thole J, Voss G, Lempicki M, Thiry G. Tuberculosis (Edinb). 2020 Dec 8. doi: 10.1016/j.tube.2020.102040. Online ahead of print.
Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial.Day TA, Penn-Nicholson A, Luabeya AKK, Fiore-Gartland A, Du Plessis N, Loxton AG, Vergara J, Rolf TA, Reid TD, Toefy A, Shenje J, Geldenhuys H, Tameris M, Mabwe S, Bilek N, Bekker LG, Diacon A, Walzl G, Ashman J, Frevol A, Sagawa ZK, Lindestam Arlehamn C, Sette A, Reed SG, Coler RN, Scriba TJ, Hatherill M; TBVPX-203 study team. Lancet Respir Med. 2020 Dec 8. doi: 10.1016/S2213-2600(20)30319-2. Online ahead of print.
Evaluation of the effect of T regulatory cell depletion and donor BCG vaccination on Mycobacterium tuberculosis H37Ra infection using an in vitro model of human PBMC infection. Bhavanam S, Rayat GR, Keelan M, Kunimoto D, Drews SJ.Pathog Dis. 2020 Dec 9. doi: 10.1093/femspd/ftaa068.
BCG Vaccination of Infants Confers Mycobacterium tuberculosis Strain-Specific Immune Responses by Leukocytes. Subbian S, Singh P, Kolloli A, Nemes E, Scriba T, Hanekom WA, Kaplan G. ACS Infect Dis. 2020 Dec 11. doi: 10.1021/acsinfecdis.0c00696. Epub 2020 Nov 23.
Immunological basis of early clearance of Mycobacterium tuberculosis infection: the role of natural killer cells. Abebe F. Clin Exp Immunol. 2020 Dec 14. doi: 10.1111/cei.13565. Online ahead of print.
Protective efficacy of an attenuated Mtb deltaLprG vaccine in mice. Martinot AJ, Blass E, Yu J, Aid M, Mahrokhian SH, Cohen SB, Plumlee CR, Larocca RA, Siddiqi N, Wakabayashi S, Gardner M, Audette R, Devorak A, Urdahl KB, Rubin EJ, Barouch DH. PLoS Pathog. 2020 Dec 14. doi: 10.1371/journal.ppat.1009096. eCollection 2020 Dec.
Preclinical evaluation of tuberculosis vaccine candidates: Is it time to harmonize study design and readouts for prioritizing their development? Flores-Valdez MA, Segura-Cerda CA. Vaccine. 2020 Dec 14. doi: 10.1016/j.vaccine.2020.11.073. Online ahead of print.
Systematic evaluation of Mycobacterium tuberculosis proteins for antigenic properties identifies Rv1485 and Rv1705c as potential protective subunit vaccine candidates. Wang Y, Li Z, Wu S, Fleming J, Li C, Zhu G, Chen B, Ren B, Wang X, Du B, Li P, Hu P, Yang J, Liu Y, Zhou C, Zhang XE, Bi L, Zhang H, Yang J, Zhang Z. Infect Immun. 2020 Dec 14. doi: 10.1128/IAI.00585-20. Online ahead of print.
Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis. Bellini C, Horváti K.Cells. 2020 Dec 15. doi: 10.3390/cells9122673.
Efficient 5-OP-RU-Induced Enrichment of Mucosa-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 Dec 15. doi: 10.1128/IAI.00524-20. Print 2020 Dec 15.
A Review of Adherence and Predictors of Adherence to the CONSORT Statement in the Reporting of Tuberculosis Vaccine Trials. Ngah VD, Mazingisa AV, Zunza M, Wiysonge CS. Vaccines (Basel). 2020 Dec 16. doi: 10.3390/vaccines8040770.
The immune landscape in tuberculosis reveals populations linked to disease and latency.Esaulova E, Das S, Singh DK, Choreño-Parra JA, Swain A, Arthur L, Rangel-Moreno J, Ahmed M, Singh B, Gupta A, Fernández-López LA, de la Luz Garcia-Hernandez M, Bucsan A, Moodley C, Mehra S, García-Latorre E, Zuniga J, Atkinson J, Kaushal D, Artyomov MN, Khader SA. Cell Host Microbe. 2020 Dec 16. doi: 10.1016/j.chom.2020.11.013. Online ahead of print.
Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis.Montalvo-Quirós S, Vallet-Regí M, Palacios A, Anguita J, Prados-Rosales RC, González B, Luque-Garcia JL. Pharmaceutics. 2020 Dec 16. doi: 10.3390/pharmaceutics12121218.
Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India. Yadav RM, Dalvi A, Gupta M, Bargir UA, Shabrish S, Aluri J, Kulkarni M, Hule G, Kambli P, Setia P, Jodhawat N, Taur P, Desai M, Madkaikar MR. Scand J Immunol. 2020 Dec 16. doi: 10.1111/sji.13010. Online ahead of print.
Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis. Tantivitayakul P, Juthayothin T, Ruangchai W, Smittipat N, Disratthakit A, Mahasirimongkol S, Tokunaga K, Palittapongarnpim P. Heliyon. 2020 Dec 18. doi: 10.1016/j.heliyon.2020.e05744. eCollection 2020 Dec.
Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice.Gupta SK, Parlane NA, Luo D, Rehm BHA, Heiser A, Buddle BM, Wedlock DN. Sci Rep. 2020 Dec 18. doi: 10.1038/s41598-020-79407-7.
Mycobacterium ulcerans-specific immune response after immunisation with bacillus Calmette-Guerin (BCG) vaccine. Pittet LF, Tebruegge M, Dutta B, Donath S, Messina N, Casalaz D, Hanekom WA, Britton WJ, Robins-Browne R, Curtis N, Ritz N; BCG Immune Response Study (BIRS) group. Vaccine. 2020 Dec 25. doi: 10.1016/j.vaccine.2020.11.045. Online ahead of print.