The Severe Acquired Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has had an unprecedented impact on our understanding and awareness of the continuous threat of emerging infectious diseases. Coronavirus disease 2019 (Covid-19), caused the death of more than seven million individuals (1, 2) The World Health Organization (WHO) has estimated mortality rates to be approximately 15 million deaths over three years (3). In addition, Covid-19 led to a sudden increase in incidences of numerous other communicable and non-communicable diseases (4). One disease that was been profoundly affected is tuberculosis (TB) (5). This was due to multiple factors, notably the disruption of laboratory services, shortages of drug supply, and deviation of funding and personnel to diagnosis and care of Covid-19 patients. During the height of the Covid-19 crisis, TB morbidity and mortality increased for the first time in the 21st century to 10-11 million new cases and 1.6 million deaths in 2021 (5). It has been estimated that over the last 200 years, TB has been the cause of one billion deaths averaging annual mortality in the order of five million deaths over 200 years, similar to the estimated five million annual deaths caused by Covid-19 over three years (5–9). It is now clear that TB patients after successful therapy can develop post-TB, which not only affects the lungs but can also lead to other disabilities, notably neurological and cardiac impairments. The Covid-19 crisis led to reduced case findings and therapy for TB. This coincidence will likely lead to the increased appearance of post-TB. Thus, the consequences of the Covid-19 TB syndemic will have a much greater impact on health and consequently on economic losses in the years to come (10, 11). Yet, to my knowledge, there is no direct information regarding the impact of Covid-19 on post-TB.

As soon as the pandemic potential of SARS-CoV-2 became apparent, multiple efforts were undertaken to develop and deploy Covid-19 vaccines at unprecedented speed (6). Research and development (R&D) of Covid-19 vaccines could build on knowledge gathered in the aftermath of the emergence of SARS-CoV-1 and the Middle East Respiratory Syndrome (MERS) virus, even though these coronaviruses had been brought under control by conventional public health measures (12). Through these efforts, it became clear that the Spike protein mediates virus attachment to and entry into host cells and that blocking the viral attachment by neutralizing antibodies represents a key protective mechanism (13).

Supported by virtually unlimited funding, the research and development (R&D) of SARS-CoV-2 vaccines was pursued at accelerated speed through remarkable collaborations between scientific communities across continents (14). Furthermore, adoptive trial design, streamlined regulatory processes, expedited regulatory review and rapid emergency use approval made vaccine rollout possible within less than one year (15). Complemented by scaled-up manufacturing capacities, millions of lives could be saved. The mRNA encapsulated in lipid nanoparticles (LNP) turned out the most efficacious vaccine platform (16). Although this platform was a new aspect of the vaccine portfolio, its manufacturing could be scaled up rapidly. In total, more than 13 billion doses were deployed in record time, nearly fulfilling the demands of the industrialized world. This scenario, however, was overshadowed by inequitable access to vaccines in low- and middle-income countries (17).

Vaccine R&D in general has benefited from the example of the Covid-19 vaccine pipeline in several instances. First, virtually unlimited investment into novel vaccines in the very beginning does not only save lives but also generates a return on investment (14, 18, 19). A study in New York provides an illustrative example by showing that 10 US$ was saved for every 1 US$ invested in vaccination against Covid-19 (19). Second, adoptive trials combining safety and efficacy assessments are feasible (20). Third, accelerated regulatory processes as well as provisional authorization for emergency use act as accelerators. Fourth, vaccine rollout at a large scale in high-income countries proved that logistic, manufacturing, and deployment hurdles can be overcome. Fifth, the speed of vaccine development can be markedly accelerated by sharing data and samples. Sixth, vaccines need to be made available across continents including low- and middle-income countries (17). As a corollary, R&D centers as well as manufacturing facilities, complemented by an infrastructure that guarantees adequate education, trust, and expertise in the global south are needed to ensure a robust supply chain for equitable access to vaccines (17, 21).

Applying the lessons learned in recent vaccine R&D will enable a more rapid response against future emerging diseases with pandemic potential. This will also promote vaccine R&D against diseases that already pose an enormous threat and for which efficacious vaccines are not yet available, such as Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS), malaria, Hepatitis C, Dengue, and TB. There will be no strategy that fits all; thus, specific modifications are critical for each vaccination strategy under development. It is also unclear whether the new mRNA : LNP vaccine type, which was so successful in the case of Covid-19, can be applied to infectious diseases that are chronic and controlled by complex cell-mediated rather than humoral immunity, such as TB.

This article briefly discusses the major vaccine platforms in general terms (section 2), summarizes the major Covid-19 vaccines (section 3), and reviews immunity in TB (section 4). It then discusses different vaccination regimes and hurdles for vaccine R&D relevant to TB (section 5) before describing the pipeline of TB vaccines in clinical trials in more detail (section 6). The final sections examine which lessons from Covid-19 vaccine R&D could benefit the TB vaccine portfolio and what approach TB research needs to undertake (sections 7 and 8).

Vaccines can be divided into subunit vaccines or whole-cell vaccines (22). To ensure induction of adequate immunity, major subunit vaccine platforms comprise: (i) well-defined antigen(s) formulated in adjuvant, (ii) mRNA encoding such antigen(s) and packaged in LNP (mRNA : LNP), or (iii) bacterial or viral vectors expressing such antigen(s). Whole-cell vaccines are either inactivated non-viable or attenuated viable vaccines. They more or less comprise all antigens of the pathogen independent of their role in protective immunity.

Roughly one year after the introduction of the first vaccines against Covid-19, numerous vaccines had been rolled out in different regions of the globe and more than 11 vaccines have been granted emergency use listing (EUL) by the WHO (37). These include inactivated whole cell vaccines, viral-vectored vaccines, protein:adjuvant vaccines, and mRNA : LNP vaccines. Some of these vaccines had been approved in a large number of states, notably for emergency use; others had received approval in only a few countries. In the following, a brief description of the most widely used vaccines granted EUL by the WHO is provided ( Figure 1 ).

The inactivated whole cell vaccines Covilo and CoronaVac by Sinopharm or Sinovac, respectively, had been approved rapidly in China and received permission for emergency use in other countries (38, 39). Both vaccines had been inactivated with beta-propiolactone and formulated in alum salt as adjuvant to stimulate neutralizing antibodies (40). These vaccines probably possess low T cell stimulatory activity because of the exclusive use of alum and they would likely benefit from a T cell stimulating adjuvant. In contrast, the inactivated vaccine VLA2001 of Valneva is formulated in alum salt plus CpG as a TLR-9 agonist, thereby stimulating both humoral and cellular immune responses (41). Similarly, Covaxin from Bharat Biotech contains inactivated SARS-CoV-2 formulated in alum adsorbed TLR-7/TLR-8 agonist (42).

Ad has been the preferred vector system for the expression of the Spike protein. These include human Ad26 and Ad5 as well as the chimpanzee Ad, ChAdOx (30). These Ad serotypes were chosen to avoid rapid inactivation of the carrier by pre-existing antibodies induced by circulating Ad serotypes. The prevalence of Ad26 and Ad5 in humans is low and ChAdOx does not circulate in humans. To avoid the generation of novel virus particles in the immunized host, the Ad vectors have been rendered non-replicative. The ChAdOx vaccine (Vaxzevria from Oxford AstraZeneca, COVISHIELD from Serum Institute of India) given as homologous prime/boost, has been broadly deployed (42, 43). The Ad26-based vaccine JCOVDEN from Janssen (Johnson & Johnson) and the Ad5-based vaccine Convidecia from CanSino Biologics are considered single shot vaccines (44, 45).

The protein:adjuvant vaccine (Nuvaxovid from Novavax, COVOVAX from Serum Institute of India) had received emergency use in several countries (40, 46). This vaccine is composed of protein nanoparticles (similar to virus-like particles) incorporated in the Matrix-M adjuvant containing saponin and based on ISCOM.

Within less than a year, the mRNA : LNP vaccines turned out to be most efficacious with the frontrunners produced by Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) (34, 47, 48). The mRNA : LNP vaccines comprise a modified mRNA encoding part of the Spike protein as an antigen. The mRNA : LNP vaccines do not only stimulate neutralizing antibodies but also T cell responses that recognize conserved epitopes in the Spike protein, which are broadly shared with various coronaviruses including circulating viruses and novel variants of SARS-CoV-2. Hence, they elicit protective immunity against severe disease even in cases in which the highly specific antibodies fail to adequately neutralize new mutations in the Spike protein.

In summary, the major lessons learned from the R&D of the Covid-19 vaccines can be summarized as follows:

The development of effective Covid-19 vaccines was an outstanding success story. Yet, in the long-term, a universal pan-corona vaccine providing long-term protection would be extremely valuable. Such next generation vaccines should induce an immune response comprising:

Figure 2 schematically summarizes protective immunity elicited by SARS-CoV-2 infection and by mRNA : LNP vaccines against Covid-19.

Establishment of infection ( Figure 3 ): TB is primarily a disease of the lung that also serves as the main port of entry for the causative agent, Mycobacterium tuberculosis (Mtb) (57, 58). TB is transmitted via aerosols, coughed up by a patient with active TB although other modes of transmission are possible. Pathogens transmitted via the aerogenic route enter the lung alveoli within small aerosol particles which provide some shield for Mtb. Bacteria are engulfed by alveolar macrophages, tissue-resident mononuclear phagocytes with the capacity for self-renewal. In addition, notably after the onset of inflammation and attracted by chemokines and other attractants, neutrophils, and monocytes enter alveoli from the blood circulation, which are capable of engulfing Mtb (59). The pathogen is transported to different sites of the lung parenchyma by mononuclear phagocytes. At the site of Mtb deposition, granulomas begin to develop independently from each other (60, 61). Some Mtb may be killed by the phagocytes soon after infection, notably in individuals who have been immunized with BCG and/or carry latent TB infection (LTBI). In this situation, macrophages could develop trained immunity based on epigenetic changes (62). Evidence for the participation of natural killer (NK) cells in early defense against Mtb has been presented (63). These NK cells are rapidly attracted to the Mtb-infected lung. It is a matter of discussion whether early infection control can lead to sterile eradication in so-called non-converters (see 5.1).

Initiation of the acquired immune response ( Figure 3 ): Interstitial dendritic cells (DC) transport Mtb to draining lymph nodes and chemokines attract additional DC as well as T lymphocytes and B lymphocytes into specialized structures in the lymph node, where the acquired immune response is activated (64–66). CD4 T cells of Th1 type, which produce multiple cytokines, are considered of critical importance (67). The role of CD4 T cells in controlling TB is probably best illustrated by the aggravated outcome of HIV-Mtb coinfection (68). HIV impairs CD4 T cells and people living with HIV (PLWH) are highly susceptible to TB (69). Interferon-γ (IFN-γ) and tumor necrosis factor α (TNFα) are of major importance as they activate mononuclear phagocytes directly (70, 71). The critical role of TNFα in controlling Mtb in infected individuals became obvious when patients with rheumatoid arthritis treated with anti-TNF monoclonal antibodies frequently progressed to active TB (72). IL-2 could contribute to protection by activating other lymphocyte subsets, notably CD8 T cells. In addition to Th1 cells, also Th17 producing cells are considered important, notably at the early stage of infection (73, 74). CD4 T cells are restricted by the major histocompatibility complex class II (MHC II) and hence are primarily focused on macrophages and DC. CD8 T lymphocytes contribute to protection via the secretion of IFN-γ and TNFα. In addition, they also directly attack infected host cells by means of perforin and granzyme. Moreover, human CD8 T cells produce granulysin which has been shown to directly kill Mtb (75–77). Because of their MHC I restriction, CD8 T cells possess a much broader target spectrum than CD4 T cells (78, 79). Hence, they monitor virtually all nucleated cells, e.g. epithelial cells surrounding alveoli, which can harbor Mtb.

Unconventional T cells are potential contributors to defense against Mtb including (80, 81):

These populations are considered donor-unrestricted since they recognize non-peptidic epitopes in the context of unconventional presentation molecules that lack the heterogeneity of canonical MHC molecules that restrict conventional T cell responses (87). The innate lymphoid cells (ILC) are characterized by the absence of T cell receptor (TCR) and hence do not recognize antigens at all (88, 89). They are present in mucosal surfaces and at tissue sites such as the lung and likely participate in the early defense against Mtb. Similar to Th lymphocytes, ILC segregates into subtypes according to their cytokine profile. Hence, by producing IFN-γ and TNFα or IL-17, ILC contributes to protective immunity in TB, notably during the early stages. NK cells can be viewed as ILC since they lack the TCR and are of lymphoid origin (63). Yet, they are not tissue resident and circulate through the blood stream. In conclusion, the role of conventional T cells in TB is well accepted, whereas the participation of unconventional T cells and ILC remains less well understood.

B lymphocytes first play a role in TB by regulating immune responses, mostly by means of cytokines (90, 91). Second, they are the cellular source of antibodies (92). Antibodies can support protective immunity by facilitating phagocytosis, formation of phagosome/lysosome fusion, and stimulation of reactive oxygen and nitrogen intermediates (92–96). Indeed, evidence had already been presented in the 1970s that antibodies mediating the uptake of Mtb through the FcR promote phagosome/lysosome fusion for bactericidal activities (97, 98). Another role of antibodies in TB is the arming of NK cells. Evidence has been presented that NK cells can kill infected cells via ADCC (63).

Immunity during LTBI ( Figure 3 ): The description of the different cell populations should not be interpreted to mean that these cells act independently; rather, they crosstalk with each other and it is this complex interplay between the different cells of the innate and acquired arm of immunity and their secretion products (notably cytokines, chemokines, and antibodies), which results in protective immunity capable of containing Mtb and thus preventing progression to active TB (99–102). At the risk of oversimplification, fine-tuned immunity controls the infection and at the same time keeps inflammation at a minimum. This is the case with LTBI which affects one quarter of the world population. Maladapted immunity fails to control infection and inflammation, thereby allowing progression to active TB ( Figure 3 ). This complex immune response is highly sensitive to perturbations. Notably, in the absence of correlates of protection (see 5.5.2), the mechanisms underlying effective host control in 90% of individuals infected with Mtb and progression to active TB disease in 10% of these remain elusive. Notably, it is unclear whether this failure is due to exhaustion or active downregulation of the protective immune components ( Figure 3 ). Obviously, efficacious vaccines against TB need to induce a fine-tuned immune balance (58, 103, 104).

Because Mtb interferes with the buildup of protective immunity, it takes several weeks before granulomatous lesions develop into solid granulomas that contain Mtb. Within these granulomas, different populations of Mtb-specific lymphocytes, mononuclear phagocytes, DC, and other cell types exist in a well-organized structure. T lymphocytes will develop into memory T cells, which segregate into effector memory T cells, central memory T cells, and resident memory T cells (105–107). Resident memory T cells seem to be of particular importance (108). Active granulomas can induce the formation of lymphoid follicles in their vicinity, which participate in the orchestration of the solid granuloma (99, 109, 110).

Progression to necrotic and caseous granulomas ( Figure 3 ): A maladapted immune response promotes the transition of solid granulomas to necrotic and then caseous granulomas (59, 103, 104). This progression from LTBI to active TB disease can occur months to years after infection. The maladaptation may be caused by exogenous factors such as coinfection with HIV or helminths or through endogenous factors, which can be summarized as suppression and exhaustion. The latter mechanisms are still incompletely understood. It is likely that suppressive mononuclear phagocytes, the myeloid derived suppressor cells (MDSC), regulatory B cells, and regulatory T cells contribute to the transition into necrotic/caseous granulomas (90, 111–113). Moreover, evidence has been presented for the role of checkpoint control in TB, e.g. through interactions between programmed cell death protein 1 (PD-1) and ligand for PD-1 (PDL-1) or between T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and ligand of TIM-3 (TIM-3L) (114, 115). Evidence suggests that blocking checkpoint control in TB causes excessive immunity characterized by elevated TNF-α production further emphasizing the importance of fine-tuned immunity in TB control and of maladapted immunity as a critical factor of active TB disease (116). The deteriorating immune response in the granulomas causes marked cell destruction, leading to loss of structure and function. In parallel, the lack of granuloma structure allows access of Mtb to capillaries that facilitate transmission to other organs in the body and to alveoli, which promote spread into the environment. At this stage, patients suffer from active TB and are contagious.

During their residence in the solid granuloma, Mtb organisms are mostly in a dormant stage, i.e. they show low to absent metabolic and replicative activity (64, 117, 118). Once the immune response worsens and caseous granulomas develop Mtb ‘wakes up’ and transits into a replicative and metabolic active stage. The cellular detritus in the caseous granuloma favors Mtb growth. The switch from dormant to active Mtb could have consequences for the selection of vaccine antigens (117, 119). Vaccines targeting the prevention of infection (PoI) in naïve individuals could benefit from active Mtb antigens, whereas vaccines targeting the prevention of disease (PoD) in LTBI would exploit dormant Mtb antigens. Consistent with this, a preponderance of dormancy associated antigens has been identified in individuals with LTBI (120).

Vaccines for both PoI (reinfection) and PoD in individuals with LTBI will require both types of antigens.

The granuloma landscape in the lung is heterogeneous (61, 99). During the early stages of LTBI, lesions of different developmental stages coexist which will then mature into solid granulomas (121). During progression to active TB, granulomas transit into the necrotic and then caseous stage. Hence, during incipient/pre-clinical TB, necrotic lesions emerge. This seems to induce an increased inflammatory response which can be determined in the blood by means of transcriptomic and metabolomic biosignatures, which can be harnessed for prognosis of active TB (122–126).

Figure 4 describes the major stages from infection to disease in TB, which serve as targets for intervention by TB vaccines currently under clinical assessment. In the following, different vaccination strategies relevant to TB control, and the value of correlates and surrogates of protection, which are still missing for TB, but availability for Covid-19 will be discussed (119).

The devastating health crisis created by Covid-19 provided pivotal lessons for future epidemic, endemic, and pandemic control measures at all levels including vaccine R&D for TB. Lessons of general relevance include the need for stronger healthcare systems, improved infection control measures, better preparedness and resilience to emerging and existing health threats, and better public health education.

More specific guidelines from the Covid-19 crisis that are relevant for TB vaccine R&D include, financial support for TB vaccine R&D is of critical importance. At present, support is still insufficient despite a slight increase over the last decade, costing approximately $1 billion US dollars per year (175). The immediate support by public, philanthropic, and private partners for Covid-19 vaccine R&D up to $100 billion US dollars (14). This unprecedented funding demonstrates the impact that early financial investment can have on vaccine R&D for health. It has to be voiced more clearly that in the long run, investment in TB vaccine R&D will pay back (176). The current financial burden of TB has been estimated in the order of $100 billion US dollars annually. Hence, public-philanthropic-private partnerships should be formed if the industry hesitates to invest in TB vaccines because of assumed low profit. A recent example of a philanthropic-private partnership is the handing over of the TB vaccine, M72:AS01_E, for phase II/III clinical trial testing from GlaxoSmithKline to the Bill and Melinda Gates Foundation and the Wellcome Trust (177).

The global response to the Covid-19 crisis fostered a stronger collaborative spirit among researchers from both public and private entities, which profoundly accelerated vaccine development. This lesson should be applied to improve joint research and resource mobilization for TB vaccine R&D. A recent example is the head-to-head phase III clinical trial performed by the Indian Council of Medical Research to compare protection against TB by the attenuated vaccine, VPM1002, and the inactivated vaccine, Immuvac (178). In a similar vein, late stage vaccine trials should not only aim to provide information on the vaccine candidate under trial but also to generate information for the informed design of next-generation vaccine candidates.

The transition from preclinical to clinical studies has frequently been termed the ‘valley of death’ due to the many obstacles that can occur. During the Covid-19 crisis, the regulatory processes for vaccines were markedly expedited by streamlined regulatory processes to mitigate such obstacles, at least partially. TB vaccine R&D could similarly benefit from streamlined regulatory processes without any curtailment in safety and efficacy standards (20). Related to this, adaptive clinical trial design can further contribute to accelerated clinical vaccine testing (15, 134). Both strategies can speed up the clinical development pipeline without compromising safety and efficacy standards.

Once a better efficacy and/or safety profile for a novel TB vaccine over BCG has been established, vaccine manufacturing capacity will become a critical factor (179). Hence, appropriate manufacturing capacities need to be established early on: at the latest, in parallel to a phase III vaccine trial. Since this is best accomplished by facilities with high manufacturing capacity meeting global demands, appropriate partnerships need to be established and investment into expanded manufacturing capabilities needs to be mobilized. The Covid-19 pandemic provides lessons, some of which should be followed and others modified or avoided. A positive example is the agreement between the startup company BioNTech and the big pharma company Pfizer to develop, test, and deploy Comirnaty as fast as possible. On the other hand, the COVAX enterprise ultimately failed to achieve equitable vaccine distribution across the globe (180, 181).

Another important aspect of this topic is equitable access to TB vaccines at low cost, which needs to be guaranteed for low- and middle-income countries, not the least because they face the highest TB burden (17, 182). One step towards this could be the establishment of vaccine manufacturing capacities in regions where TB vaccines are needed most. This strategy includes not only manufacturing capacities but also strong educational and training activities to ensure successful TB vaccine production and deployment from local manufacturers (21). The largest vaccine manufacturer by dose is the Serum Institute of India Pvt. Ltd., which is based in India, a country with a high prevalence of TB. For regions without manufacturing capacities, the founding of WHO mRNA vaccine hubs on the African continent provides precedent from the Covid-19 field for this strategy (183).

Covid-19 vaccination campaigns have highlighted the importance of robust surveillance and monitoring systems that track the effectiveness and adverse events of the newly deployed vaccines. These lessons need to be adopted in modified form for TB from rollout to long-term surveillance of vaccines, notably since long-term protection is essential for TB control.

The impact of Covid-19 vaccination programs has saved millions of lives. Yet, in a small proportion of the global population, in both the North and the South, vaccine hesitancy and even aggressive vaccine opposition arose (184). Many diverse reasons account for vaccine hesitancy and denial including distrust of traditional political authorities (185). Hence, multidimensional approaches will be required to mitigate these challenges (186, 187). Successful TB vaccine rollout needs to be accompanied by a build-up in public trust through engaging and educating communities that suffer from high TB burden and addressing their concerns.

A major game changer emerged during the Covid-19 vaccine crisis, namely the creation of viral-vectored and mRNA : LNP vaccines as novel vaccine platforms. Whilst vector-based vaccines have already been included in the TB vaccine R&D portfolio, mRNA : LNP vaccines represent a novelty. This versatile platform must be included in the TB vaccine R&D pipeline. A major vaccine developer, BioNTech, already started a phase I safety trial for mRNA : LNP vaccines that encode various TB antigens. Assuming that subunit vaccines covering a small number of antigens can target Mtb with sufficient efficiency to provide long-term protection it is likely that mRNA : LNP vaccines can become major players for TB control.

TB has been around for centuries, claiming more than a billion lives (9). Despite its threat, the TB crisis has remained largely silent. Indeed, TB morbidity and mortality have been on the decline over recent decades; yet this decline is far too meager and alone it will not enable us to reach the goal of ending TB by 2030 as proposed by the Stop TB Partnership and the WHO (188, 189). This decline even reversed with the emergence of SARS-CoV-2 with an estimated 10-11 million people acquiring active TB and 1.6 million people dying. In 2018, a High-Level Meeting of the United Nations (UN) General Assembly made a strong commitment to end TB by 2030 (190–192). To achieve the goal, the UN is committed to creating “an environment conducive to research and development for new tools for TB”. Accordingly, the commitment was made “to mobilize sufficient and sustainable financing with the aim of increasing overall global investments to 2 billion US dollars [ … ] in funding annually for tuberculosis research” (191). This noble goal was interrupted by Covid-19. Hence, in 2023, a second High-Level Meeting on TB will be convened by the UN (193).

A strong commitment to ending TB is urgently needed. Otherwise, the WHO goal of reducing TB incidence by 50% and the numbers of TB deaths by 75% between 2015 and 2025 will be missed, notably because by 2021 only 10% reduction in TB incidence and 5.9% reduction in TB deaths had been accomplished. In 2023, 30,000 people develop active TB every day and approximately 4,200 of them will die of this disease. By 2050, four million deaths will occur leading to an economic loss of $13 billion US Dollars (192). Better intervention measures are urgently needed and TB vaccines play a major role in this endeavor.

As has been discussed in this review, TB vaccine R&D cannot replicate the success story of Covid-19 vaccine R&D. Yet, by building on the experience gathered during the Covid-19 pandemic, the conditions for TB can be changed for the better. In the aftermath of the Covid-19 crisis, a working group had been established under the leadership of E.J. Sirleaf, former President of Liberia, and H. Clark, former Prime Minister of New Zealand, on ‘How an Outbreak Became a Pandemic’ under the ethos, ‘Covid-19: Make it the Last Pandemic’ (7, 8). Their concluding comment stated that their “message for change is clear: no more pandemic. If we fail to take this goal seriously, we will condemn the world to successive catastrophes”. They go on to outline how the demands of this task are “large and challenging, but the price is even larger and more rewarding. With so many lives at stake, now is the time to resolve ”. This call to prevent the next pandemic can be rephrased as task for future control of the ongoing TB pandemic: the “message for change is clear: No more TB. If we fail to take this goal seriously, we will condemn the world to continued catastrophes. The ask is large and challenging, but the price is even larger and more rewarding. With so many lives at stake, now is the time to resolve”.

SK: Conceptualization, Writing – original draft.