Bacille Calmette Research Articles

MTBVAC induces superior antibody titers and IgG avidity compared to BCG vaccination in non-human primates

The only currently licensed vaccine against tuberculosis (TB), Bacille Calmette Guérin (BCG), is insufficient to control the epidemic. MTBVAC is a live attenuated strain of Mycobacterium tuberculosis (M.tb) and is one the most advanced TB vaccine candidates in the pipeline. It is more efficacious than BCG in preclinical models including non-human primates (NHPs), and has demonstrated safety and immunogenicity in human populations. To better understand the immune mechanisms underlying the superior efficacy conferred by MTBVAC, we characterized M.tb-specific antibody responses in NHPs vaccinated with either BCG or MTBVAC. MTBVAC vaccination induced higher titers of IgG, IgM and IgA, and higher avidity IgG compared with BCG vaccination. IgG avidity correlated with protection following M.tb challenge in the same animals, validating the association previously reported between this measure and protection in the context of intravenous BCG vaccination, suggesting that IgG avidity may represent a relevant marker or correlate of protection from TB.

Regional Lymphadenitis Related to Bacille Calmette–Guerin Vaccination: A Case Series from a Tertiary Care Childrens’ Hospital

Background: Immunization with Bacille Calmette–Guerin (BCG) vaccine, used worldwide for years, for the prevention of tuberculosis, rarely leads to complications like regional lymphadenitis. There is controversy regarding the management of BCG lymphadenitis. We share our experience regarding the management and course of this rare complication in nine infants. Clinical Description: Over a period of 24 months, 9 infants, who had received BCG vaccination after birth, presented to us between 1 and 3 months of age, with left-sided supraclavicular swellings. The infants were otherwise thriving well, with no constitutional symptoms. On examination, the infants were stable with normal systemic examination. Local examination revealed all the swellings to be supraclavicular lymphadenopathies, two of them being suppurative. Thus, the infants fulfilled the clinical criteria for BCG regional lymphadenitis. Management and Outcome: Fine-needle aspiration cytology from the swellings of all infants was consistent with BCG lymphadenitis. Two of the smears were positive for acid-fast bacilli. Besides percutaneous pus aspiration in two infants, no other intervention was done in any of the infants, and no antibiotics nor antitubercular treatment was administered. With observation and regular follow-up, the lymphadenopathies resolved over time in all the infants. Conclusion: This case series creates awareness regarding the benign, self-resolving nature of BCG regional lymphadenitis, which may be followed conservatively without any medical or surgical intervention.

Low-dose M.tb infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates.

Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund's Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied. We set out to evaluate antibody responses to a range of unrelated pathogens following infection with Mycobacterium tuberculosis (M.tb) and vaccination with BCG or a candidate TB vaccine, MTBVAC, in non-human primates. We demonstrate a significant increase in the titer of antibodies against SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, tetanus toxoid, and respiratory syncytial virus antigens following low-dose aerosol infection with M.tb. The magnitude of some of these responses correlated with TB disease severity. However, vaccination with BCG administered by the intradermal, intravenous or aerosol routes, or intradermal delivery of MTBVAC, did not increase antibody responses against unrelated pathogens. Our findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies.

An intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis

Mucosal vaccines have the potential to elicit protective immune responses at the point of entry of respiratory pathogens, thus preventing even the initial seed infection. Unlike licensed injectable vaccines, mucosal vaccines comprising protein subunits are only in development. One of the primary challenges associated with mucosal vaccines has been identifying and characterizing safe yet effective mucosal adjuvants that can effectively prime multi-factorial mucosal immunity. In this study, we tested NanoSTING, a liposomal formulation of the endogenous activator of the stimulator of interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as a mucosal adjuvant. We formulated a vaccine based on the H1 antigen (fusion protein of Ag85b and ESAT-6) adjuvanted with NanoSTING. Intranasal immunization of NanoSTING-H1 elicited a strong T-cell response in the lung of vaccinated animals characterized by (a) CXCR3+ KLRG1− lung resident T cells that are known to be essential for controlling bacterial infection, (b) IFNγ-secreting CD4+ T cells which is necessary for intracellular bactericidal activity, and (c) IL17-secreting CD4+ T cells that can confer protective immunity against multiple clinically relevant strains of Mtb. Upon challenge with aerosolized Mycobacterium tuberculosis Erdman strain, intranasal NanoSTING-H1 provides protection comparable to subcutaneous administration of the live attenuated Mycobacterium bovis vaccine strain Bacille–Calmette–Guérin (BCG). Our results indicate that NanoSTING adjuvanted protein vaccines can elicit a multi-factorial immune response that protects from infection by M. tuberculosis.

Effect of HIV-Integrated Care on Uptake of Maternal Health and Routine Childhood Immunization Services at Primary Health Care Facility in Northern Nigeria: An Interrupted Time Series Analysis

Background: This study assessed the effect of HIV-integrated care delivered within routine primary health care (PHC) in Kano, Nigeria, on the uptake of maternal health and routine childhood immunization services. Methods: A retrospective cohort design was used to review and collect anonymized data from medical records of women and children who accessed health care from the PHC facility between January 2009 and December 2016. Data were analyzed using SPSS version 22. Interrupted time series analysis (ITS) was performed to estimate changes in maternal and childhood immunization service usage over time following the delivery of the integrated care. Results: Uptake of maternal health services increased over time: antenatal care attendance (effect/month [95% confidence interval (CI)]: 6.6 [44.55–8.65], P = 0.0001), family planning (effect/month [95% CI]: 1.3 [0.26–2.26], P = 0.014), and delivery (effect/month [95% CI]: 0.9 [0.39–1.45], P = 0.0009). Uptake of routine immunization also increased over time with the integrated care: Bacille Calmette Guerin (BCG) (Effect/month [95% CI]: 1.8 [0.64–2.88], P = 0.002), and diphtheria, tetanus, and pertussis 1 (DPT1)/Penta 1 vaccinations (Effect/month [95% CI]: 1.0 [0.20–1.73], P = 0.013) also showed a moderate increase over time, but DPT3/Penta 3 vaccination dropped gradually over time (Effect/month [95% CI]: −0.1 [−0.74–0.46], P = 0.649). Conclusion: The integrated care resulted in increased uptake of both maternal health and childhood routine immunization services. This suggests that the reorganization and restructuring of the HIV-integrated care in the Kumbotso Comprehensive Health Centre has had a positive impact on non-HIV services provided at the center. There are still opportunities for further research to refine and elaborate on the novel findings of this study.

Prediction of Non-Muscle Invasive Papillary Urothelial Carcinoma Relapse from Hematoxylin-Eosin Images Using Deep Multiple Instance Learning in Patients Treated with Bacille Calmette-Guérin Immunotherapy.

The limited reproducibility of the grading of non-muscle invasive papillary urothelial carcinoma (NMIPUC) necessitates the search for more robust image-based predictive factors. In a cohort of 157 NMIPUC patients treated with Bacille Calmette-Guérin (BCG) immunotherapy, we explored the multiple instance learning (MIL)-based classification approach for the prediction of 2-year and 5-year relapse-free survival and the multiple instance survival learning (MISL) framework for survival regression. We used features extracted from image patches sampled from whole slide images of hematoxylin-eosin-stained transurethral resection (TUR) NPMIPUC specimens and tested several patch sampling and feature extraction network variations to optimize the model performance. We selected the model showing the best patient survival stratification for further testing in the context of clinical and pathological variables. MISL with the multiresolution patch sampling technique achieved the best patient risk stratification (concordance index = 0.574, p = 0.010), followed by a 2-year MIL classification. The best-selected model revealed an independent prognostic value in the context of other clinical and pathologic variables (tumor stage, grade, and presence of tumor on the repeated TUR) with statistically significant patient risk stratification. Our findings suggest that MISL-based predictions can improve NMIPUC patient risk stratification, while validation studies are needed to test the generalizability of our models.

Bacille Calmette–Guerin Vaccine May Be an Effective Tool for COVID-19 Prevention

Bacille Calmette–Guerin Vaccine May Be an Effective Tool for COVID-19 Prevention

Research progress in the off-target effects of Bacille Calmette-Guérin vaccine.

Bacille Calmette-Guérin (BCG) vaccine is designed to provide protection against tuberculosis (TB). However, numerous epidemiological, clinical, and immunological studies have shown that BCG vaccination affects neonatal and infant mortality, which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine. We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases, as well as the potential mechanism and influencing factors. Literature was retrieved mainly from PubMed using medical subject headings "BCG, variations, and non-specific, heterologous or off-target". Studies have showed that BCG vaccination can prevent various heterologous infections, including respiratory tract infections, leprosy, and malaria, treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy, and improve the immune responses as vaccine adjuvant. Besides, BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer, and may provide protection against autoimmune diseases. These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity, which were found to be sex-differentiated and affected by the BCG vaccine strains, sequence or time of vaccination.

Childhood immunization uptake determinants in Kinshasa, Democratic Republic of the Congo: ordered regressions to assess timely infant vaccines administered at birth and 6-weeks

BackgroundDespite global efforts to reduce preventable childhood illness by distributing infant vaccines, immunization coverage in sub-Saharan African settings remains low. Further, timely administration of vaccines at birth—tuberculosis (Bacille Calmette–Guérin [BCG]) and polio (OPV0)—remains inconsistent. As countries such as Democratic Republic of the Congo (DRC) prepare to add yet another birth-dose vaccine to their immunization schedule, this study aims to improve current and future birth-dose immunization coverage by understanding the determinants of infants receiving vaccinations within the national timeframe.MethodsThe study used two ordered regression models to assess barriers to timely BCG and first round of the hepatitis B (HepB3) immunization series across multiple time points using the Andersen Behavioral Model to conceptualize determinants at various levels. The assessment leveraged survey data collected during a continuous quality improvement study (NCT03048669) conducted in 105 maternity centers throughout Kinshasa Province, DRC. The final sample included 2398 (BCG analysis) and 2268 (HepB3 analysis) women-infant dyads living with HIV.ResultsBetween 2016 and 2020, 1981 infants (82.6%) received the BCG vaccine, and 1551 (68.4%) received the first dose of HepB3 vaccine. Of those who received the BCG vaccine, 26.3%, 43.5%, and 12.8% received BCG within 24 h, between one and seven days, and between one and 14 weeks, respectively. Of infants who received the HepB3 vaccine, 22.4% received it within six weeks, and 46% between six and 14 weeks of life. Many factors were positively associated with BCG uptake, including higher maternal education, household wealth, higher facility general readiness score, and religious-affiliated facility ownership. The factors influencing HepB3 uptake included older maternal age, higher education level, household wealth, transport by taxi to a facility, higher facility general and immunization readiness scores, and religious-affiliated facility ownership.ConclusionsThis study demonstrated that the study participants’ uptake of vaccines was consistent with the country average, but not in a timely manner. Various factors were associated with timely uptake of BCG and HepB3 vaccines. These findings suggest that investment to strengthen the vaccine delivery system might improve timely vaccine uptake and equity in vaccine coverage.

Delivery of Mycobacterium tuberculosis epitopes by Bordetella pertussis adenylate cyclase toxoid expands HLA-E-restricted cytotoxic CD8+ T cells.

Tuberculosis (TB) remains the first cause of death from infection caused by a bacterial pathogen. Chemotherapy does not eradicate Mycobacterium tuberculosis (Mtb) from human lungs, and the pathogen causes a latent tuberculosis infection that cannot be prevented by the currently available Bacille Calmette Guerin (BCG) vaccine, which is ineffective in the prevention of pulmonary TB in adults. HLA-E-restricted CD8+ T lymphocytes are essential players in protective immune responses against Mtb. Hence, expanding this population in vivo or ex vivo may be crucial for vaccination or immunotherapy against TB. The enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid is an effective tool for delivering peptide epitopes into the cytosol of antigen-presenting cells (APC) for presentation and stimulation of specific CD8+ T-cell responses. In this study, we have investigated the capacity of the CyaA toxoid to deliver Mtb epitopes known to bind HLA-E for the expansion of human CD8+ T cells in vitro. Our results show that the CyaA-toxoid containing five HLA-E-restricted Mtb epitopes causes significant expansion of HLA-E-restricted antigen-specific CD8+ T cells, which produce IFN-γ and exert significant cytotoxic activity towards peptide-pulsed macrophages. HLA-E represents a promising platform for the development of new vaccines; our study indicates that the CyaA construct represents a suitable delivery system of the HLA-E-binding Mtb epitopes for ex vivo and in vitro expansion of HLA-E-restricted CD8+ T cells inducing a predominant Tc1 cytokine profile with a significant increase of IFN-γ production, for prophylactic and immunotherapeutic applications against Mtb.

Influence of women empowerment on childhood (12–23 months) immunization coverage: Recent evidence from 17 sub-Saharan African countries

BackgroundThere is a global consensus that child immunization plays an important role in promoting the health and well-being of children. Despite the quintessential role of immunization, not all children receive full immunization coverage. We examined the association between women empowerment and childhood immunization coverage in sub-Saharan Africa (SSA).MethodsThe most recent Demographic and Health Survey data of 17 SSA countries were used for the analysis, with a sample of 19,223. The outcome and exposure variables were full immunization coverage and women empowerment, respectively. Full immunization was computed from percentage of children between the ages of 12 and 23 months who had received the following vaccines at any point in time: one dose of Bacille Calmette–Guérin, three doses of the vaccine protecting against diphtheria, pertussis, and tetanus or the tetravalent/pentavalent vaccine, three doses of the polio vaccine, and one dose of the measles vaccine (either as a standalone measles vaccine or as part of a combination with other immunogens). Women’s empowerment was an index of labour participation, acceptance towards spousal violence, decision-making capacity and general knowledge level. Descriptive analysis and multilevel logistic regression were performed. Results were reported in adjusted odds ratio with a corresponding 95% confidence interval.ResultsThe study found that 56.6% of children were fully immunized. Children of employed mothers were 1.16 times more likely to be fully immunized. Children of mothers with higher acceptance toward violence were less likely to be fully immunized [aOR = 0.90, CI 0.81, 0.99]. The odds of full immunization were higher among children born to mothers with high [aOR = 1.11, CI 1.01, 1.22] decision-making capacity. Higher odds of full immunization were found among children born to mothers with medium [aOR = 1.24, CI 1.13, 1.36] to high [aOR = 1.44, CI 1.27, 1.63] general knowledge level.ConclusionsWe conclude that empowering women through livelihood empowerment interventions can increase their decision-making capacity and foster their resolve to ensure the full immunization of their children. This can be achieved by consciously investing in initiatives such as vocational training programs, job placement services, or support for entrepreneurship initiatives to encourage and support women's workforce participation.

Hippophae rhamnoides reverses decreased CYP2D6 expression in rats with BCG-induced liver injury

In this study, we investigated the effect of Hippophae rhamnoides L. (HRP) on the activity of CYP2D6 via the CAMP/PKA/NF-κB pathway in rats with Bacille Calmette–Guerin (BCG)-induced immunological liver injury. BCG (125 mg/kg) was injected to establish the rat model of liver injury. HRP was administered intragastrically for one week as the intervention drug. Proteomics techniques were used to analyze protein expression levels, obtaining a comprehensive understanding of the liver injury process. ELISA or western blotting was used to detect specific protein levels. Dextromethorphan was detected using high-performance liquid chromatography to reflect the metabolic activity of CYP2D6. BCG downregulated the expression of CYP2D6, cAMP, PKA, IκB, and P-CREB and upregulated that of NF-κB, IL-1β, TNF-α, and CREB in the liver; HRP administration reversed these effects. Therefore, HRP may restore the metabolic function of the liver by reversing the downregulation of CYP2D6 through inhibition of NF-κB signal transduction and regulation of the cAMP/PKA/CREB/CYP2D6 pathway. These findings highlight the role of HRP as an alternative clinical drug for treating hepatitis B and other immune-related liver diseases.

Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique.

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis (Mtb) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size (n = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB.

Immune interaction between SARS-CoV-2 and Mycobacterium tuberculosis.

SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients simultaneously diagnosed with COVID-19 and tuberculosis (TB). There is a need to understand the immune interaction between SARS-CoV-2 and Mtb which impacts poor outcomes for those co-infected. We performed a PubMed and preprint search using keywords [SARS-CoV-2] AND [tuberculosis] AND [Immune response], including publications after January 2020, excluding reviews or opinions. Abstracts were evaluated by authors for inclusion of data specifically investigating the innate and/or acquired immune responses to SARS-CoV-2 and Mtb in humans and animal models, immunopathological responses in co-infection and both trials and investigations of potential protection against SARS-CoV-2 by Bacille Calmette Guérin (BCG). Of the 248 articles identified, 39 were included. Incidence of co-infection is discussed, considering in areas with a high burden of TB, where reported co-infection is likely underestimated. We evaluated evidence of the clinical association between COVID-19 and TB, discuss differences and similarities in immune responses in humans and in murine studies, and the implications of co-infection. SARS-CoV-2 and Mtb have both been shown to modulate immune responses, particularly of monocytes, macrophages, neutrophils, and T cells. Co-infection may result in impaired immunity to SARS-CoV-2, with an exacerbated inflammatory response, while T cell responses to Mtb may be modulated by SARS-CoV-2. Furthermore, there has been no proven potential COVID-19 clinical benefit of BCG despite numerous large-scale clinical trials.

Intralesional immunotherapy with Bacille Calmette- Guerin (BCG) vaccine for the treatment of cutaneous warts

Myriad of therapeutic modalities for warts are available but none promises complete response. Despite adequate treatment, the virus may persist in the surrounding tissues leading to recurrence. Immunotherapy is considered better than destructive options where there are multiple lesions, extensive involvement and is best suitable for paediatric patients. The aim of the study was to evaluate the efficacy and safety of intralesional BCG vaccine in the management of cutaneous warts (common warts, plantar and periungual warts). Patients of age 12 years and above clinically diagnosed with cutaneous warts and presenting consecutively in the outdoor clinic of Dermatology, Venereology & Leprosy Department of Dr. R.P. Govt. Medical College, Kangra at Tanda, Himachal Pradesh between June 2021 to May 2022 were enrolled. BCG vaccine was administered into the largest wart intralesionally and the injection was repeated every 3 weeks for a maximum of four injections or till the complete clearance of warts, whichever was earlier. The efficacy was assessed every 3 weeks and patients were followed up at 3 and 6 months. Majority of patients were in the age group of 14-53 years. The study showed therapeutic response in 35.08% (20/57) patients and partial response in 63.15% (36/57) patients while there was no response in 1.75% (1/57) patients at the end of 12 weeks with a very low recurrence rate (5.2%). Plantar warts have responded excellently showing complete clearance in 91.5% and partial response in 9.5% of the patients followed by palmar warts achieving complete response in 60% and partial response in 40% of the patients. The reconstituted BCG immunotherapy is a cheap, effective and easily available therapeutic option which can easily be practised routinely. However, due its considerable adverse effects as compared to other immunotherapeutic agents, we do not recommend it to be the first line agent.

Routine Immunization Uptake and Knowledge of Caregivers in Selected Rural Communities in Northwestern Nigeria

Context: Childhood immunization remains a public health problem in Nigeria, as the status did not improve substantially during the last two decades, especially in northern Nigeria. Understanding the level of routine immunization uptake of children among caregivers is important if a healthy community is to be maintained. Aim: This study aimed to investigate the knowledge and level of routine immunization uptake among caregivers in Bukkuyum Local Government of Zamfara State, Nigeria. Settings and Design: A descriptive cross-sectional study involving 320 caregivers selected using a multistage sampling technique was conducted. Materials and Methods: Sociodemographics, vaccination details, and knowledge were obtained via a semi-structured interviewer-administered questionnaire. Statistical Analysis Used: Data collected was analyzed using Statistical Package for Social Sciences (SPSS) statistics for Windows, version 21.0. Results: Findings show abysmally low levels of uptake of routine immunization antigens, namely, Bacille Calmette- Guerine (BCG) (26.1%), Oral Polio Vaccine LGAs= Local Government Areas (OPV) (42.5%), pentavalent vaccine (18.9%), and measles (13.0%). Only 80 (25.0%) children were fully immunized, 93 (29.0%) partially immunized, and 147 (46.0%) nonimmunized. Most respondents had poor knowledge (308 (96.2%)) and poor attitudinal disposition (173 (54.1%)) toward routine immunization. Conclusion: The vaccination uptake and knowledge of immunization among caregivers in the study area are poor. Caregivers' continual health education and a step-up of mobile health education activities by healthcare providers are crucial to improve routine immunization uptake in the study area.

Intravenous BCG Vaccination of Diversity Outbred Mice Results in Moderately Enhanced Protection against Challenge with Mycobacterium tuberculosis Compared to Intradermal Vaccination.

Tuberculosis is still the leading cause of death globally from any infectious disease, despite the widespread use of the live attenuated vaccine Bacille Calmette Guerin (BCG). While BCG has some efficacy against disseminated TB disease in children, protection wanes into adulthood resulting in over 1.8 million TB deaths per year. This has led to efforts to develop novel vaccine candidates that either replace or boost BCG, as well as to test novel delivery mechanisms to enhance BCG's efficacy. Traditional BCG vaccination is performed as an intradermal (ID) injection but delivering BCG by an alternate route may enhance the depth and breadth of protection. Previously, we demonstrated that phenotypically and genotypically disparate Diversity Outbred (DO) mice have heterogenous responses to M. tuberculosis challenge following intradermal BCG vaccination. Here, we utilize DO mice to examine BCG-induced protection when BCG is delivered systemically via intravenous (IV) administration. We find that DO mice vaccinated with IV BCG had a greater distribution of BCG throughout their organs compared to ID-vaccinated animals. However, compared to ID-vaccinated mice, M. tuberculosis burdens in lungs and spleens were not significantly reduced in animals vaccinated with BCG IV, nor was lung inflammation significantly altered. Nonetheless, DO mice that received BCG IV had increased survival over those vaccinated by the traditional ID route. Thus, our results suggest that delivering BCG by the alternate IV route enhances protection as detected in this diverse small animal model.

Bacille Calmette-Guerin Scar Reactivation: A Sign to Suggest Kawasaki Disease.

Bacille Calmette-Guerin Scar Reactivation: A Sign to Suggest Kawasaki Disease.

Intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis

Abstract Mucosal vaccines have the potential to elicit protective immune responses at the point of entry of respiratory pathogens thus preventing even the initial seed infection. Unlike licensed injectable vaccines, mucosal vaccines comprising protein subunits are only in the development stage. One of the primary challenges associated with mucosal vaccines has been the identification and characterization of safe yet effective mucosal adjuvants that can effectively prime multi-factorial mucosal immunity. In this study, we tested NanoSTING, a liposomal formulation of the endogenous activator of the stimulator of interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as a mucosal adjuvant. Intranasal administration of this vaccine provides protection comparable to subcutaneous administration of the live attenuated Mycobacterium bovis vaccine strain Bacille–Calmette–Guérin (BCG) upon challenge with aerosolized Mycobacterium tuberculosis Erdman strain. Protection against the bacterium is likely due to CXCR3+ lung resident T cells that are known to be important for the control of bacterial infection. Intranasal delivery also induces IFNγ secreting CD4+ T cells in lung which is necessary for intracellular bactericidal activity. Our results indicate that NanoSTING adjuvanted protein vaccines can elicit a multi-factorial immune response that provides durable protection from infection by M. tuberculosis.

Intravesical BCG therapy with photodynamic diagnosis-guided transurethral resection of bladder tumors improves recurrence-free survival

BackgroundIntravesical Bacille Calmette–Guerin (BCG) therapy has been reported to be effective in preventing recurrence and progression in non-muscle invasive bladder cancer. Furthermore, photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) improves the accuracy of cancer diagnosis and contributes to lower recurrence rates. The purpose of this study is to investigate whether more tumor resection with PDD-TURBT rather than conventional TURBT before BCG therapy outweighs the benefit of BCG therapy alone. MethodsPatients who underwent intravesical BCG therapy following TURBT in our institution from 2010 to 2021 were included. They were divided into the following two groups: those who received PDD-TURBT before BCG treatment (PDD + BCG group) and those who received conventional TURBT before BCG treatment (WL + BCG group). The 2-year recurrence-free survival (RFS) and progression-free survival (PFS) of the two groups were retrospectively analyzed and compared. ResultsThe 2-year RFS was significantly improved in the PDD + BCG group (hazard ratio [HR]: 2.41, 95% confidence interval [CI]: 1.26–4.60; p = 0.025). No significant difference in 2-year PFS was noted between the two groups. Analysis of prognostic factors for RFS showed that PDD-TURBT w We think that this text does not adequately express the meaning that we want to deliver to the reader.as a significant prognostic factor in univariate analysis (HR: 0.41, 95% CI: 0.18–0.92; p = 0.03). ConclusionBCG treatment following PDD-TURBT significantly improved RFS more than BCG therapy following WL-TURBT. More accurate tumor localization and more efficient tumor resection by PDD-TURBT may have a positive impact on subsequent BCG treatments even if the treatment is administered postoperatively.