Needle-like structures discovered on positively charged lightning branches.

Lightning is a dangerous yet poorly understood natural phenomenon. Lightning forms a network of plasma channels propagating away from the initiation point with both positively and negatively charged ends-called positive and negative leaders1. Negative leaders propagate in discrete steps, emitting copious radio pulses in the 30-300-megahertz frequency band2-8 that can be remotely sensed and imaged with high spatial and temporal resolution9-11. Positive leaders propagate more continuously and thus emit very little high-frequency radiation12. Radio emission from positive leaders has nevertheless been mapped13-15, and exhibits a pattern that is different from that of negative leaders11-13,16,17. Furthermore, it has been inferred that positive leaders can become transiently disconnected from negative leaders9,12,16,18-20, which may lead to current pulses that both reconnect positive leaders to negative leaders11,16,17,20-22 and cause multiple cloud-to-ground lightning events1. The disconnection process is thought to be due to negative differential resistance18, but this does not explain why the disconnections form primarily on positive leaders22, or why the current in cloud-to-ground lightning never goes to zero23. Indeed, it is still not understood how positive leaders emit radio-frequency radiation or why they behave differently from negative leaders. Here we report three-dimensional radio interferometric observations of lightning over the Netherlands with unprecedented spatiotemporal resolution. We find small plasma structures-which we call 'needles'-that are the dominant source of radio emission from the positive leaders. These structures appear to drain charge from the leader, and are probably the reason why positive leaders disconnect from negative ones, and why cloud-to-ground lightning connects to the ground multiple times.

Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression.

BACKGROUND: Enzyme replacement therapy (ERT) slows disease progression of Fabry disease (FD), especially when initiated before the onset of irreversible organ damage. However, with the clinically asymptomatic progression of renal, cardiac and cerebral disease manifestations spanning decades, optimal timing of ERT initiation remains unclear. METHODS: In this cross-sectional retrospective study, seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were evaluated after 10 years of treatment (median age at evaluation 24 years, range 14-26). Cardiac imaging (echocardiography and MRI), electrophysiological and biochemical data of these patients were compared to those of untreated male cFD patients (n = 23, median age 22 years, range 13-27). RESULTS: Albuminuria was less common and less severe in treated patients (albumin to creatinine ratio, ACR 0-8.8 mg/mmol, median 0.4) compared to untreated patients (ACR 0-248 mg/mmol, median 3.7, p = 0.02). The treated group had a lower left ventricular mass, measured using echocardiography (median 80 g/m2 versus 94 g/m2, p = 0.02) and MRI (median 53 g/m2 versus 68 g/m2, p = 0.02). Myocardial fibrosis was absent in all included patients. eGFR was normal in all treated patients whereas 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ. CONCLUSIONS: Start of treatment with ERT before age 16, in male cFD patients is associated with reduced occurrence of renal and cardiac manifestations of FD, as assessed by intermediate endpoints. Confirmation that this approach delays or even prevents renal failure and cardiac events requires another decade of follow-up.

A large light-mass component of cosmic rays at 10(17)-10(17.5) electronvolts from radio observations.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo.

Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation. Here we observed that AT1413 binds also to certain non-hematopoietic tumor cells, particularly melanoma and breast cancer. AT1413 immune precipitated CD43s from melanoma cells confirming that it recognizes the same target on melanoma as on AML. AT1413 induced antibody-dependent cellular cytotoxicity against short-term cultured patient-derived melanoma samples. However, AT1413 was unable to affect the growth of melanoma cells in vivo. To increase the efficacy of AT1413 as a therapeutic antibody, we generated two different formats of bispecific T-cell engaging antibodies (TCEs): one binding bivalently (bTCE) and the other monovalently (knob-in-hole; KiH) to both CD43s and CD3ε. In vitro, these TCEs redirected T-cell cytotoxicity against melanoma cells with differences in potencies. To investigate their effects in vivo, we grafted mice that harbor a human immune system with the melanoma cell line A375. Treatment with both AT1413 bTCE and AT1413 KiH significantly reduced tumor outgrowth in these mice. These data indicate a broad therapeutic potential of AT1413 that includes AML and CD43s-expressing solid tumors that originate from CD43-negative tissues.

[Waiting for death: an analysis of the waiting list of the expertise centre for euthanasia]. / Wachten op de dood: een analyse van de wachtlijst van Expertisecentrum Euthanasie.

BACKGROUND: The waiting list of the expertise center euthanasia (EE) in the Netherlands for patients requesting euthanasia on the basis of psychiatric suffering has increased to two years in a short space of time. AIM: Clarity about the causes and direct consequences of the EE waiting list and an answer to the question: what now? METHOD: We analyzed the EE waiting list based on various media reports, annual reports from the EE and scientific studies. RESULTS: The EE waiting list arose because, on the one hand, the demand for euthanasia among patients with a mental illness has increased, while on the other hand, the willingness to perform euthanasia among psychiatrists appears to be declining. The reasons for both trends seem multifactorial. The direct consequence of the waiting list is that patients with a mental illness have less access to euthanasia, which in itself can also have harmful and protective consequences. CONCLUSION: The EE waiting list is the result of an increasing number of requests and an apparent decrease in psychiatrists' willingness to perform euthanasia. In response to this situation, roughly three ways forward are conceivable: first the mental health care sector can assign itself a more active role in the field of euthanasia, second a further demedicalisation of the end of life is possible, or third a choice can be an amendment to EE's referral procedure. All of these options have potential pros and cons.

[Towards a proactive psychiatric ethics: a care ethics perspective]. / Naar een proactieve psychiatrische ethiek: een zorgethisch perspectief.

Background Proactive psychiatry requires proactive psychiatric ethics. Aim To describe ethical considerations with regard to proactive psychiatry. Method Discussion of care ethics aimed at proactive psychiatric care. Results In this contribution, we plea for a proactive psychiatric ethics, stimulating and supporting healthcare professionals in working from a developmental and contextual perspective. We describe care ethics, and show that it is in line with the principles of proactive psychiatry. We address three issues related to the development of proactive psychiatry: the goals of care; identifying risk factors; and the division of responsibilities in mental healthcare. Conclusion Proactive psychiatric ethics can be useful in identifying and discussing ethical issues associated with proactive psychiatry and thus contribute to improving practice. Tijdschrift voor Psychiatrie 63(2021)2, 150-153.

Radio Emission Reveals Inner Meter-Scale Structure of Negative Lightning Leader Steps.

We use the Low Frequency Array (LOFAR) to probe the dynamics of the stepping process of negatively charged plasma channels (negative leaders) in a lightning discharge. We observe that at each step of a leader, multiple pulses of vhf (30-80 MHz) radiation are emitted in short-duration bursts (<10 µs). This is evidence for streamer formation during corona flashes that occur with each leader step, which has not been observed before in natural lightning and it could help explain x-ray emission from lightning leaders, as x rays from laboratory leaders tend to be associated with corona flashes. Surprisingly, we find that the stepping length is very similar to what was observed near the ground, however with a stepping time that is considerably larger, which as yet is not understood. These results will help to improve lightning propagation models, and eventually lightning protection models.

ATP13A2/PARK9 regulates endo-/lysosomal cargo sorting and proteostasis through a novel PI(3, 5)P2-mediated scaffolding function.

ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2. We found that under proteotoxic stress conditions, evoked by the proteasome inhibitor Bortezomib, endo-/lysosomal associated full-length ATP13A2 WT, catalytically-inactive or N-terminal fragment mutants, reduced the intracellular accumulation of ubiquitin-conjugated (Ub) proteins, independent of autophagic degradation. In contrast, ATP13A2 silencing increased the intracellular accumulation of Ub-proteins, a pattern also observed in patient-derived fibroblasts harbouring ATP13A2 loss-of function mutations. In treated cells, ATP13A2 evoked endocytic vesicle relocation and increased cargo export through nanovesicles. Expression of an ATP13A2 mutant abrogating PI(3,5)P2 binding or chemical inhibition of the PI(3,5)P2-generating enzyme PIKfyve, compromised vesicular trafficking/nanovesicles export and rescued intracellular accumulation of Ub-proteins in response to proteasomal inhibition. Hence, our study unravels a novel activity-independent scaffolding role of ATP13A2 in trafficking/export of intracellular cargo in response to proteotoxic stress.

Antibodies against recombinant alpha-galactosidase A in Fabry disease: Subclass analysis and impact on response to treatment.

BACKGROUND: Treatment of Fabry disease (FD) with recombinant alpha-galactosidase A (r-αGAL A) is complicated by the formation of anti-drug antibodies in the majority of male patients with the classical disease phenotype. Detailed information regarding antibody subtypes, onset and persistence of antibody development and their effect on treatment efficacy is sparse. METHODS: A retrospective study was carried out in 39 male patients with classical FD, treated with either agalsidase-alfa or agalsidase-beta (mean follow up of 10 years). With six to twelve months intervals plasma-induced in vitro inhibition of enzyme activity, lysoglobotriaosylsphingosine (lysoGb3) levels and renal function were assessed. In a subset of 12 patients, additionally anti- r-αGAL A IgM, IgA and IgG1, 2, 3 and 4 levels were analyzed. RESULTS: In 23 out of 39 patients, plasma-induced in vitro inhibition of r-αGAL A activity was observed (inhibition-positive). The inhibition titer was strongly negatively correlated to the decrease in lysoGb3: agalsidase-alfa (FElog10(inhibition) = -10.3, P ≤.001), agalsidase-beta (FElog10(inhibition) = -4.7, P ≤.001). Inhibition-positive patients had an accelerated decline in renal function (FE = 1.21, p = .042). During treatment IgG1 anti-r-αGAL A levels increased only in inhibition-positive patients (p = .0045). IgG4 anti-r-αGAL A antibodies developed in 7 out of 9 inhibition-positive patients. Other antibody subclasses were either not present or too low to quantify. CONCLUSION: Development of inhibiting antibodies against r-αGAL A negatively affects the biochemical response to ERT and resulted in an accelerated decline in renal function. The presence of IgG1 and IgG4 anti-r-αGAL A antibodies is associated with in vitro αGAL A activity inhibition.

Multilingualism was associated with lower cognitive outcomes in children who were born very and extremely preterm.

AIM: This study determined whether cognitive outcomes differed between very preterm (VPT) and extremely preterm (EPT) children who were monolingual or multilingual when they reached the corrected ages of two and five years. METHODS: The data were collected at the Emma Children's Hospital, Amsterdam, The Netherlands, as part of our national neonatal follow-up programme and comprised 325 VPT/EPT children born between January 1, 2007 and January 1, 2012. The study used the Third Editions of the Bayley Scales of Infant and Toddler Development and the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: We compared 234 monolingual children, 65 multilingual children who spoke Dutch and at least one foreign language at home and 26 multilingual children who didn't speak Dutch at home. The best performers on the cognitive scale at two years of age and the verbal subscales at five years of age were the monolingual children, followed by the children who spoke Dutch and at least one foreign language at home, then the children who only spoke foreign languages at home. CONCLUSION: In our study cohort from The Netherlands, multilingualism lowered the cognitive and verbal outcomes of VPT/EPT children at the corrected ages of two and five years.

[Euthanasia of Dutch psychiatric patients in 2015-2017]. / Euthanasie van Nederlandse psychiatrische patiënten in 2015-2017.

BACKGROUND: The Netherlands is one of the few countries in the world that allows euthanasia and assisted suicide (EAS) due to psychiatric suffering. METHODS In 2015-2017 the Dutch regional euthanasia review committees published 43 case summaries online. Of these, 35 were suitable for analysis regarding patient characteristics and physician involvement, and 3 cases were described in detail.
RESULTS: In total, 77% of the patients were women and 51% were aged 50-70 years. Major depression disorder and personality disorders were present in almost half of the patients. All patients were considered mentally competent. CONCLUSIONS Although the incidence of psychiatric EAS cases is rising, we found no shift in patient characteristics. The division between psychiatric and somatic suffering may prove more complicated than expected. Patients dying from suicide differ in various ways from patients dying through EAS. The fact that all patients are considered competent could mean that they are unjustly seen as being vulnerable or that the competence assessment lacks due diligence.

Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta-analysis.

OBJECTIVE: To establish, based on a systematic literature review, the frequency of pathogenic submicroscopic chromosomal aberrations in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, with the aim of determining whether high-resolution testing for submicroscopic aberrations is beneficial in a general pregnant population. METHODS: EMBASE, PubMed, Web of Science and CENTRAL databases were searched systematically on 3 June 2016 for all relevant articles on the prevalence of pathogenic submicroscopic copy number variants (CNVs) in fetuses referred for prenatal invasive testing because of advanced maternal age (AMA) or parental anxiety (ANX). Relevant full-text articles were analyzed and the prevalence of submicroscopic CNVs was calculated based on the extracted data. Meta-analysis was conducted in a pooled cohort of 10 614 fetuses based on the 10 largest studies (n > 300) of a total of 19 that were relevant. RESULTS: Pooled estimate analysis indicated that 0.84% (95% CI, 0.55-1.30%) of fetuses that had invasive testing because of AMA/ANX carried a pathogenic clinically significant submicroscopic aberration. The onset/penetrance of submicroscopic findings was studied in 10 314 fetuses reported in eight papers that presented aberrant cases with all necessary details to allow assessment of the findings. The pooled estimates resulting from meta-analysis of the data indicated that an early-onset syndromic disorder was detected in 0.37% (95% CI, 0.27-0.52%) of cases, a susceptibility CNV was found in 0.30% (95% CI, 0.14-0.67%) and late-onset diseases were reported in 0.11% (95% CI, 0.05%-0.21%). The prevalence of early-onset syndromic disorders caused by a submicroscopic aberration was calculated to be 1:270. When the risk for submicroscopic aberrations is added to the individual risk for microscopic chromosomal aberrations, all pregnant women have a risk of higher than 1 in 180 for a relevant chromosomal aberration, and pregnant women under 36 years of age have a higher risk for submicroscopic pathogenic aberrations than for Down syndrome. CONCLUSION: This systematic review shows that a significant proportion of fetuses in a general pregnant population carry a submicroscopic pathogenic CNV. Based on these figures, all women should be informed on their individual risk for all pathogenic chromosomal aberrations and not only for common trisomies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Exploring the predictive power of interaction terms in a sophisticated risk equalization model using regression trees.

This study explores the predictive power of interaction terms between the risk adjusters in the Dutch risk equalization (RE) model of 2014. Due to the sophistication of this RE-model and the complexity of the associations in the dataset (N = ~16.7 million), there are theoretically more than a million interaction terms. We used regression tree modelling, which has been applied rarely within the field of RE, to identify interaction terms that statistically significantly explain variation in observed expenses that is not already explained by the risk adjusters in this RE-model. The interaction terms identified were used as additional risk adjusters in the RE-model. We found evidence that interaction terms can improve the prediction of expenses overall and for specific groups in the population. However, the prediction of expenses for some other selective groups may deteriorate. Thus, interactions can reduce financial incentives for risk selection for some groups but may increase them for others. Furthermore, because regression trees are not robust, additional criteria are needed to decide which interaction terms should be used in practice. These criteria could be the right incentive structure for risk selection and efficiency or the opinion of medical experts.

[Is psychiatry ready to let patients review their own files? Inventory of initial experiences]. / Is de psychiatrie klaar voor de meelezende patiënt? Inventarisatie van eerste ervaringen.

BACKGROUND: Dutch patients will be granted the right to digitally access their own medical records, an option already available to the patients at the University Medical Center Utrecht since 2015. AIM: To start a conversation about the development of readily accessible online patient records. METHODS Describe the experiences of a University department of psychiatry with an online patient portal, obtained through discussions and questionnaires. RESULTS: During the next few years three legal developments will enable patients to acquire direct, remote, digital access to their medical files. Immediate online review of medical records improves accessibility and empowers the patient. Some therapists experienced a change in patient interaction. Furthermore, during documentation psychiatrists took into account that patients could review the contents at a later point. CONCLUSION: Patients' accessibility of online records will influence the patient-therapist dynamic. More research on the patient perspective and a discussion among professionals are necessary to further streamline broad implementation of online patient portals.

Prenatal and postnatal findings in small-for-gestational-age fetuses without structural ultrasound anomalies at 18-24 weeks.

OBJECTIVE: To assess phenotypic and genotypic characteristics of small-for-gestational-age (SGA) fetuses without structural anomalies at 18-24 weeks' gestation. METHODS: This retrospective study included structurally normal singleton fetuses with an abdominal circumference ≤ 5th percentile on detailed ultrasound examination between 18 and 24 weeks' gestation. Cases were stratified according to the absence or presence of other abnormal ultrasound findings, such as abnormal amniotic fluid or soft markers. All patients were offered invasive prenatal testing with rapid aneuploidy detection by qualitative fluorescence polymerase chain reaction (QF-PCR) and, if normal, consecutive single nucleotide polymorphism (SNP) array was also offered. Detailed postnatal follow-up (≥ 5 months) was performed. In cases in which a syndromic phenotype became apparent within 5 months after birth and SNP array had not been performed prenatally, it was performed postnatally. RESULTS: A total of 211 pregnancies were eligible for inclusion. Of the 158 cases with isolated SGA on ultrasound, 36 opted for invasive prenatal testing. One case of trisomy 21 and one case of a submicroscopic abnormality (a susceptibility locus for neurodevelopmental disease) were detected. Postnatal follow-up showed a postnatal apparent syndromic phenotype in 10 cases. In one case this was due to trisomy 21 and the other nine (5.8%; 95% CI, 2.8-10.0%) cases had normal SNP array results. In 32/53 cases with SGA and associated ultrasound abnormalities, parents opted for invasive testing. One case of trisomy 21 and one of triploidy were found. In 11 cases a syndromic phenotype became apparent after birth. One was due to trisomy 21 and in one case a submicroscopic anomaly (a susceptibility locus) was found. The remaining syndromic cases (17.3%; 95% CI, 8.7-29.0%) had normal SNP array results. CONCLUSION: Testing for chromosomal anomalies should be offered in cases of SGA between 18 and 24 weeks' gestation. Whole chromosome anomalies occur in 1.3% (95% CI, 0.2-3.9%) of isolated SGA and 5.8% (95% CI, 1.5-14.0%) of associated SGA. In 0.6% (95% CI, 0.1-2.8%) and 1.9% (95% CI, 0.2-8.2%), respectively, SNP array detected a susceptibility locus for neurodevelopmental disease that would not be detected by karyotyping, QF-PCR or non-invasive prenatal testing. Therefore, and because the genetic causes of SGA are diverse, we suggest SNP array testing in cases of SGA. Thorough postnatal examination and follow-up of infants that presented with reduced fetal growth is important because chromosomally normal syndromic phenotypes occur frequently in SGA fetuses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Psychopathology in families: an integral approach via the family outpatient clinic]. / Psychiatrische stoornissen binnen gezinnen: een integrale benadering via de familiepoli.

BACKGROUND: Psychiatric disorders run in families. To bridge the gap between child and youth psychiatry and adult psychiatry, GGZ inGeest has started screening parents of new registered children for psychopathology - and if indicated - offers parents treatment in the same department as their children. AIM: To examine the feasibility and usefulness of this procedure, to investigate how many parents agree to screening, further diagnostics and treatment, and to find out how many parents have in fact suffered from recent psychiatric problems. METHOD: Prior to the children's first appointment, the parents were asked to complete a questionnaire, the Adult Self Report (ASR), about their own problems. If these scores were (sub)clinical, parents were invited to participate in a telephonic interview. This consisted of the Composite International Diagnostic Interview (CIDI) and Conners' Adult ADHD Rating Scales (CAARS). If the results indicate psychopathology, further psychiatric assessment and, if necessary, treatment is offered. RESULTS: The first response was 55.7% and, if indicated, most of the parents agreed on further diagnostics. On the ASR 2 out of 5 mothers (42.1%) and 1 out of 5 fathers (21.8%) reported problems that could point to a psychiatric disorder. According to the ASR, within this high-risk group 37% of the mothers met the criteria for an axis I diagnosis (less than one month earlier) compared to 70.6% of the fathers. A mood disorder was the primary diagnosis for women, whereas men most often suffered from an anxiety disorder. In total, 19.1% of the parents screened were suffering from recent psychopathology and 75% of this group agreed to receive mental health care (treatment at the family outpatient clinic or referred to another clinic). CONCLUSION: Implementation of the family outpatient clinic scheme is feasible. However, further efforts are needed in order to reach a larger group of parents, particularly fathers. The family outpatient clinic is useful because parents who suffer from psychopathology do not always receive mental health care. However, a randomised control trial is needed to determine whether parallel treatment of parents and children can improve the treatment outcome for children.

Probing Atmospheric Electric Fields in Thunderstorms through Radio Emission from Cosmic-Ray-Induced Air Showers.

We present measurements of radio emission from cosmic ray air showers that took place during thunderstorms. The intensity and polarization patterns of these air showers are radically different from those measured during fair-weather conditions. With the use of a simple two-layer model for the atmospheric electric field, these patterns can be well reproduced by state-of-the-art simulation codes. This in turn provides a novel way to study atmospheric electric fields.

Cationic pH-sensitive liposome-based subunit tuberculosis vaccine induces protection in mice challenged with Mycobacterium tuberculosis.

Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants - CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB. In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine's effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB.