Tuberculosis Vaccine Research Articles

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT.

Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear. In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine. MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group. MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.

Impact of universal tuberculosis vaccination cessation on the epidemiology of paediatric tuberculosis cases in Ireland from 2011 to 2021

BackgroundUniversal Bacillus Calmette-Guérin vaccine (BCG) vaccination was discontinued in Ireland in April 2015 due to a lack of vaccine supply. We analysed notifications from the Irish National Tuberculosis Surveillance System from 2011 to 2021 to examine the direct impact of vaccination cessation on active tuberculosis cases among young children. MethodsWe did a cross-sectional study to compare tuberculosis age-specific incidence rates (ASIRs) among children aged 0–4 years born during a period of BCG vaccination (January 2007 to March 2015) with those born after BCG vaccination cessation (April 2015 to December 2021). We calculated ASIRs using census population denominators and did a temporal trend analysis of ASIRs using negative binomial regression. Data were anonymised before use in this study so no ethical approval or patient consent was required. FindingsNo significant temporal trend was detected in ASIR by notification year during 2011–21 (incidence rate ratio [IRR] 0·98; 95% CI 0·85–1·1). However, the temporal trend for cases born during universal vaccination was significantly declining (IRR 0·72 [95% CI 0·56–0·93]) whereas cases born after vaccination ceased had a non-significant increase (1·4 [0·99–1·96]). No meningitis cases were reported during universal vaccination compared with one (5%) of 19 cases reported after vaccination ceased. The proportion of cases reported as vaccinated decreased from 58% (11 of 19) during universal vaccination to 21% (four of 19) after vaccination ceased. Six (32%) of 19 cases born after vaccination ceased would have been eligible to receive BCG under a selective programme. No significant difference in the proportion of cases associated with outbreaks was detected across the two periods. Regional ASIRs increased in two eastern regions after vaccination ceased, whereas they declined in the remaining six regions. InterpretationUniversal BCG cessation has not directly impacted on new tuberculosis cases among children aged 0–4 years. However, timely surveillance is needed to monitor the impact of vaccination cessation. A selective BCG programme might have prevented cases diagnosed in certain risk groups. FundingHealth Service Executive, Ireland.

What's Old and New in Tuberculosis Vaccines for Children.

Tuberculosis (TB) is a leading cause of global child mortality. Until the turn of the 21st century, Mycobacterium bovis bacille Calmette-Guerin (BCG) was the only vaccine to prevent TB. The pediatric TB vaccine pipeline has advanced in the past decade to include the evaluation of novel whole cell vaccines to replace infant BCG and investigation of subunit and whole cell vaccines to boost TB immunity during adolescence. We describe the history of BCG, current TB vaccine candidates in clinical trials, and the challenges and opportunities for future TB vaccine research in children. Children are a critical target population for TB vaccines, and expansion of the pediatric TB vaccine pipeline is urgently needed to end the TB pandemic.

Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis.

Vaccination is an excellent approach to stimulating the host immune response and reducing human morbidity and mortality against microbial infections, such as tuberculosis (TB). Bacillus Calmette-Guerin (BCG) is the most widely administered vaccine in the world and the only vaccine approved by the World Health Organization (WHO) to protect against TB. Although BCG confers "protective" immunity in children against the progression of Mycobacterium tuberculosis (Mtb) infection into active TB, this vaccine is ineffective in protecting adults with active TB manifestations, such as multiple-, extensive-, and total-drug-resistant (MDR/XDR/TDR) cases and the co-existence of TB with immune-compromising health conditions, such as HIV infection or diabetes. Moreover, BCG can cause disease in individuals with HIV infection or other immune compromises. Due to these limitations of BCG, novel strategies are urgently needed to improve global TB control measures. Since live vaccines elicit a broader immune response and do not require an adjuvant, developing recombinant BCG (rBCG) vaccine candidates have received significant attention as a potential replacement for the currently approved BCG vaccine for TB prevention. In this report, we aim to present the latest findings and outstanding questions that we consider worth investigating regarding novel mycobacteria-based live attenuated TB vaccine candidates. We also specifically discuss the important features of two key animal models, mice and rabbits, that are relevant to TB vaccine testing. Our review emphasizes that the development of vaccines that block the reactivation of latent Mtb infection (LTBI) into active TB would have a significant impact in reducing the spread and transmission of Mtb. The results and ideas discussed here are only based on reports from the last five years to keep the focus on recent developments.

Responses of Humoral and Cellular Immune Mediators in BALB/c Mice to LipX (PE11) as Seed Tuberculosis Vaccine Candidates.

A member of the pe/ppe gene family, lipX (pe11), is capable of directing persistent Mycobacterium tuberculosis and avoiding host immune responses. Some studies have indicated that LipX (PE11) can detect humoral antibodies in tuberculosis patients. Hence, information on immune mediators' responses to this protein is essential to understand its protective efficacy against M. tuberculosis infections. This study aimed to examine the response of immune mediators to pCDNA3.1-lipX expression in vivo. In the experiment, pCDNA3.1-lipX was injected into BALB/c strain male mice aged between 6 and 8 weeks, and they were compared to groups injected with pCDNA3.1 and without injection. The injection was carried out three times intramuscularly every two weeks. Blood was taken retro-orbitally and used for humoral response analysis by Western blotting against LipX-His protein. Simultaneously, the splenocytes were cultured and induced with LipX-His protein for cellular immunity analyses. Our study showed that the recombinant DNA of pCDNA3.1-lipX induced a humoral and cellular immune response, especially in IL-4, IL-12, and IFN-γ, which are the primary cellular responses to M. tuberculosis infections. However, additional studies, such as a challenge study, are needed to strengthen the argument that this plasmid construction is feasible as a tuberculosis seed vaccine candidate.

100 Years of BCG Immunization: Past, Present, and Future

The 100th anniversary of the introduction of Bacille-Calmette-Guérin (BCG) as a tuberculosis (TB) vaccine is an occasion warranting further investigation of the early attempts which culminated in the introduction of BCG as a TB vaccine, as well as of subsequent recognition of failures, new findings that broaden its applications, outstanding questions, and approaches towards the development of novel vaccine candidates [...].

Construction and expression of Mycobacterium tuberculosis fusion protein AR2 and its immunogenicity in combination with various adjuvants to form vaccine

Tuberculosis (TB) is recognized as a highly infectious disease worldwide, and Bacille Calmette–Guerin (BCG) remains the only TB vaccine licensed for clinical use. As there is little evidence that BCG is effective in adults, there is an urgent need for a safe and effective vaccine to control TB in adults. In this study, we tested the immunomodulatory efficiency of the fusion protein AR2.whole blood IFN-γ release assay (WBIA) was used to detect antigen specificity. The immunogenicity of the vaccine was tested in C57BL/6 mice, and confirmed by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and qRT-PCR. The fusion protein AR2 was successfully constructed and expressed. The level of IFN-γ in the peripheral blood of subjects stimulated by AR2 was significantly higher than in those induced by all subcomponent proteins. AR2-specific IgG and the Th1 cytokines IFN-γ, TNF-α, and iNOS were significantly increased in the group treated with the fusion protein and compound adjuvant (AR2+DMC). Likewise, the number of IFN-γ+ CD4+, IFN-γ+CD8+, and IL-4+ CD8+ T lymphocytes increased significantly. The combination of the fusion protein and the compound adjuvant (AR2+DMC) may be a suitable candidate for an enhanced TB vaccine. This study provides theoretical and experimental support for future research to enhance the effectiveness of TB vaccines and provides an experimental basis for evaluating the influence of different adjuvants on vaccine efficacy.

MicroRNA-31 mediated by interferon regulatory factor 7 signaling facilitates control of Mycobacterium tuberculosis infection

Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection.

Paving the way to a new class of efficient and safe tuberculosis vaccines: The role of c-di-AMP in Mycobacterium tuberculosis immunity and virulence

Tuberculosis (TB) remains a challenge and threat to public health despite being a curable and preventable infectious disease. TB is caused by a potentially serious respiratory acid-fast bacillus Mycobacterium tuberculosis (Mtb). As one of the top ten causes of death globally, the World Health Organization recently reported that more than 1.5 million people died from TB and approximately 10 million humans developed TB in 2020.1 Until the onset of the coronavirus disease 2019 (COVID-19) pandemic, TB was the leading cause of death from an infectious agent, ranking even before HIV.

Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape

Vaccinations, especially DNA vaccines that promote host immunity, are the most effective interventions for tuberculosis (TB) control. However, the vaccine delivery system exhibits a significant impact on the protective effects of the vaccine. Recently, effective nanomaterial-based delivery systems (including nanoparticles, nanogold, nanoliposomes, virus-like particles, and virus carriers) have been developed for DNA vaccines to control TB. This review highlights the historical development of various nanomaterial-based delivery systems for TB DNA vaccines, along with the emerging technologies. Nanomaterial-based vaccine delivery systems could enhance the efficacy of TB vaccination; therefore, this summary could guide nanomaterial selection for optimal and safe vaccine delivery, facilitating the design and development of highly effective TB vaccines.

Toll-like receptor-mediated innate immune responses by recognition of the recombinant dormancy-associated Mycobacterium tuberculosis proteins Rv2659c and Rv1738.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) poses a major threat to the global public health. Importantly, latent tuberculosis infection (LTBI) still impedes the elimination of TB incidence since it has a substantial risk to develop active disease. A multi-stage subunit vaccine comprising active and latency antigens of Mtb has been raised as the promising vaccine to trigger immune protection against all stages of TB. Therefore, the discovery of new antigens that could trigger broad immune response is essential. While current development of TB vaccine mainly focuses on protective immunity mediated by adaptive immune response, the knowledge on triggering the innate immune response by antigens is still limited. We showed that recombinant dormancy-associated Mtb proteins Rv2659c and Rv1738 were recognized by human innate immune recognition molecules, Toll-like receptors (TLRs) 2 and 4 by using HEK-Blue™ hTLR2/hTLR4 systems. We further demonstrated that these two proteins activated phosphorylated NF-κB p65 (Ser536) in the human CD14+ blood cells. We also investigated that these two proteins significantly induced level of pro- and anti-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10 and TNF-α) which were mediated through TLR2 and TLR4 pathways in human peripheral blood mononuclear cells (hPBMCs). These findings suggest that proteins Rv2659c and Rv1738 stimulated innate immune response targeting TLR2 and TLR4 to produce inflammatory cytokines, and their benefits would be valuable for the development of an effective prophylactic tuberculosis vaccine.

Modeling of MT. P495, an mRNA-based vaccine against the phosphate-binding protein PstS1 of Mycobacterium tuberculosis.

Tuberculosis (TB) is a contagious disease that predominantly affects the lungs, but can also spread to other organs via the bloodstream. TB affects about one-fourth population of the world. With age, the effectiveness of Bacillus Calmette-Guérin (BCG), the only authorized TB vaccine, decreases. In the quest for a prophylactic and immunotherapeutic vaccine, in this study, a hypothetical mRNA vaccine is delineated, named MT. P495, implementing in silico and immunoinformatics approaches to evaluate key aspects and immunogenic epitopes across the PstS1, a highly conserved periplasmic protein of Mycobacterium tuberculosis (Mtb). PstS1 elicited the potential to generate 99.9% population coverage worldwide. The presence of T- and B-cell epitopes across the PstS1 protein were validated using several computational prediction tools. Molecular docking and dynamics simulation confirmed stable epitope-allele interaction. Immune cell response to the antigen clearance rate was verified by the in silico analysis of immune simulation. Codon optimization confirmed the efficient translation of the mRNA in the host cell. With Toll-like receptors, the vaccine exhibited stable and strong interactions. Findings suggest that the MT. P495 vaccine probably will elicit specific immune responses against Mtb. This mRNA vaccine model is a ready source for further wet-lab validation to confirm the efficacy of this proposed vaccine candidate.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11030-022-10515-4.

Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice.

Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What’s more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults.

Immunomodulatory effect of mycobacterial outer membrane vesicles coated nanoparticles.

Tuberculosis (TB) is one of the most widely prevalent infectious diseases that cause significant mortality. Bacillus Calmette-Guérin (BCG), the current TB vaccine used in clinics, shows variable efficacy and has safety concerns for immunocompromised patients. There is a need to develop new and more effective TB vaccines. Outer membrane vesicles (OMVs) are vesicles released by Mycobacteria that contain several lipids and membrane proteins and act as a good source of antigens to prime immune response. However, the use of OMVs as vaccines has been hampered by their heterogeneous size and low stability. Here we report that mycobacterial OMVs can be stabilized by coating over uniform-sized 50nm gold nanoparticles. The OMV-coated gold nanoparticles (OMV-AuNP) show enhanced uptake and activation of macrophages and dendritic cells. Proteinase K and TLR inhibitor studies demonstrated that the enhanced activation was attributed to proteins present on OMVs and was mediated primarily by TLR2 and TLR4. Mass spectrometry analysis revealed several potential membrane proteins that were common in both free OMVs and OMV-AuNP. Such strategies may open up new avenues and the utilization of novel antigens for developing TB vaccines.

Multi Epitope-Based Vaccine Design for Protection Against Mycobacterium tuberculosis and SARS-CoV-2 Coinfection.

BackgroundA prophylactic and immunotherapeutic vaccine for Mycobacterium tuberculosis (MTB) and SARS-CoV-2 coinfection needs to be developed for a proactive and effective therapeutic approach. Therefore, this study aims to use immunoinformatics to design a multi-epitope vaccine for protection against MTB and SARS-CoV-2 coinfection.MethodsThe bioinformatic techniques were used to screen and construct potential epitopes from outer membrane protein A Rv0899 of MTB and spike glycoprotein of SARS-CoV-2 for B and T cells. The antigenicity, allergenicity, and several physiochemical properties of the developed multi-epitope vaccination were then evaluated. Additionally, molecular docking and normal mode analysis (NMA) were utilized in evaluating the vaccine’s immunogenicity and complex stability.ResultsSelected proteins and predicted epitopes suggest that the vaccine prediction can be helpful in the protection against both SARS-CoV-2 and MTB coinfection. Through docking molecular and NMA, the vaccine-TLR4 protein interaction was predicted to be efficient with a high level of IgG, T-helper cells, T-cytotoxic cells, andIFN-γ.ConclusionThis epitope-based vaccine is a potentially attractive tool for SARS-CoV-2 and MTB coinfection vaccine development.

Characterization of Mycobacterium tuberculosis-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

The development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4+ T cells producing IL-22, a distinct subset termed "Th22" cells, may contribute to protective immunity to TB. Thus, we characterized Mycobacterium tuberculosis-specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infection. We investigated the functional properties (IFN-γ, IL-22, and IL-17 production), memory differentiation (CD45RA, CD27, and CCR7), and activation profile (HLA-DR) of M. tuberculosis-specific CD4+ T cells. In HIV-uninfected individuals with latent TB infection, we detected abundant circulating IFN-γ-producing CD4+ T cells (median, 0.93%) and IL-22-producing CD4+ T cells (median, 0.46%) in response to M. tuberculosis The frequency of IL-17-producing CD4+ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4+ T cells and not coexpressed with IL-17. M. tuberculosis-specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-γ responses. M. tuberculosis-specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, M. tuberculosis-specific IL-22 was produced by conventional CD4+ T cells that required TCR engagement. In conclusion, we confirm that Th22 cells are a component of the human immune response to TB. Depletion of M. tuberculosis-specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.

Induction of Cross-Reacting Antibodies Against the COVID-19 by BCG Vaccination in the Mouse Model.

It was reported that tuberculosis and BCG vaccination are potential tools for reducing the burden of COVID-19, mainly through the non-specific trained immunity. We have investigated whether BCG vaccination is able to induce cross-reacting antibodies against the SARS-CoV-2. We have tested the induced humoral immune responses against the SARS-CoV-2 Spike in the mouse model, after either BCG or rabies DNA-based vaccination alone or in Prime/Boost approach to COVID-19 DNA-based vaccination. We have demonstrated that BCG vaccination alone was able to induce cross-reacting antibodies to SARS-CoV-2 Spike. It can also boost the antibody response induced by a COVID-19 DNA-based vaccination. Hence, both BCG and latent tuberculosis infection can explain the lower burden of COVID-19 in developing countries, not only through the trained immunity but also by inducing cross-reacting antibodies. Furthermore, with the emergence of different COVID-19 variants, or eventually other Betacoronaviruses, the use of BCG vaccination can help against immune escapes of the current vaccines.

Lower SARS-CoV-2 Seroprevalence among Cancer Patients in Sub-Saharan Africa.

Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and study variables were determined using a logistic regression analysis. Results: High seroprevalence against the SARS-CoV-2 spike and nucleocapsid proteins were found among the SARS-CoV-2 unvaccinated COVID-19 pandemic populations in SSA. However, the cancer patients demonstrated a lower seroprevalence compared to potential blood donors. There was also an association between mild COVID-19 symptoms with prior tuberculosis vaccination among cancer patients. Conclusion: Cancer patients in SSA tend to have a relatively lower SARS-CoV-2 seroprevalence compared to potential blood donors recruited from the same geographic locations during the COVID-19 pandemic. More study is required to determine its cause and potential impact on SARS-CoV-2 vaccination among cancer patients.

Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c

The vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) elicits an immune response that is protective against certain forms of tuberculosis (TB); however, because BCG efficacy is limited it is important to identify alternative TB vaccine candidates. Recently, the BCG deletion mutant and vaccine candidate BCGΔBCG1419c was demonstrated to survive longer in intravenously infected BALB/c mice due to enhanced biofilm formation, and better protected both BALB/c and C57BL/6 mice against TB-induced lung pathology during chronic stages of infection, relative to BCG controls. BCGΔBCG1419c-elicited protection also associated with lower levels of proinflammatory cytokines (i.e. IL6, TNFα) at the site of infection in C57BL/6 mice. Given the distinct immune profiles of BCG- and BCGΔBCG1419c-immunized mice during chronic TB, we set out to determine if there are early immunological events which distinguish these two groups, using multi-dimensional flow cytometric analysis of the lungs and other tissues soon after immunization. Our results demonstrate a number of innate and adaptive response differences between BCG- and BCGΔBCG1419c-immunized mice which are consistent with the latter being longer lasting and potentially less inflammatory, including lower frequencies of exhausted CD4+ T helper (TH) cells and higher frequencies of IL10-producing T cells, respectively. These studies suggest the use of BCGΔBCG1419c may be advantageous as an alternative TB vaccine candidate.

A next generation BCG vaccine moves forward

The Mycobacterium Bovis bacille Calmette–Guerin (BCG) vaccine is now over 100 years old. During this century, we have learnt a lot about what the BCG vaccination does and does not do, including that it does not provide consistent or optimal protection against tuberculosis (TB), and particularly, the most common pulmonary form of the disease, that is responsible for Mycobacterium tuberculosis transmission.1,2 Many new candidate TB vaccines are in the development pipeline, including individual antigens delivered by viral vectors or with adjuvant and live mycobacterial vaccines such as genetically modified BCG or M tuberculosis itself.