tuberculosis vaccine

Immunogenicity and protective efficacy of recombinant BCG expressing a multi-epitope vaccine against mycobacterium tuberculosis.

Zhang Xuan-Ji XJ, Luo Jia-Rui JR, Tian Ting-Ting TT, Shi Juan J et al.

Mycobacterium tuberculosis (Mtb) infects approximately one-quarter of the global population, of whom 5%-10% develop active tuberculosis (TB). Although Bacillus Calmette-Guérin (BCG) remains the cornerstone vaccine against severe infant TB, its efficacy in adults is limited, underscoring the need for novel TB vaccines. This study aimed to design a multi-epitope vaccine, tMEV, and validate its protective potential through bioinformatic prediction and in vivo experiments. tMEV was constructed from dominant T- and B-cell epitopes derived from Mtb ESAT-6, PE35, PPE38, and PE4 proteins, fused with an adjuvant. Its vaccine candidacy was assessed via physicochemical and solubility profiling, secondary and tertiary structure modeling, TLR-4 molecular docking, molecular dynamics simulation, and immune simulation. The tMEV coding sequence was cloned into pMV361 and transformed into BCG to generate recombinant BCG (rBCG-tMEV). Immunogenicity, antigenicity, and protective efficacy were evaluated in mouse immunization and Mtb challenge models. tMEV exhibited favorable vaccine-like properties in silico. In mice, both tMEV and rBCG-tMEV induced Mtb-specific immune responses. Compared with PBS, tMEV significantly enhanced cellular and humoral immunity with a Th2-biased profile. Relative to conventional BCG, rBCG-tMEV elicited a superior mixed Th1-Th2 response and higher antigen-specific immunity, accompanied by increased secretion of IFN-γ, IL-2, TNF-α, granzyme B, and perforin. Moreover, rBCG-tMEV markedly reduced bacterial loads in the lungs and spleens of Mtb-infected mice, conferring partial protection. These findings demonstrate that tMEV and rBCG-tMEV possess robust immunogenicity and protective potential against Mtb, representing promising novel TB vaccine candidates and providing a rationale for future vaccine development and optimization.

Case report: Maternal engraftment of T-cells in a patient with Severe Combined Immunodeficiency due to DCLRE1C pathogenic variant - diagnostic and treatment challenges.

Peiseniece Evija E, Rozevska Marija M, Arnite Viktorija V, Rascon Jelena J et al.

Severe combined immunodeficiency (SCID) is a rare but serious congenital condition caused by genetic defects that severely impair the development and function of T cells, B cells, and natural killer (NK) cells. Without early diagnosis and immune system reconstitution, SCID is usually fatal in infancy. The condition requires prompt recognition and hematopoietic stem cell transplantation (HSCT) to restore immune function. This report describes the first genetically confirmed case of SCID in Latvia - caused by a DCLRE1C gene pathogenic variant and diagnosed prior to the implementation of national newborn screening for SCID - complicated by disseminated tuberculosis following Bacillus Calmette-Guérin (BCG) vaccination. The male infant was born after an uneventful pregnancy to healthy parents with no known genetic disorders. The patient experienced recurrent bacterial respiratory infections and received the first scheduled vaccination, the BCG vaccine, at 2 months of age, later than recommended in the national immunization schedule because of parental hesitancy related to concerns about vaccine safety. Shortly after receiving the BCG vaccine, the infant developed erythroderma and a maculopapular rash, followed by pneumonia, acute bronchiolitis, and a bacterial skin infection at three months of age. Immunological evaluation revealed an atypical pattern for SCID, with CD3+ T cells at 53% (abs. 764/μL) and CD4+ T cells at 52% (abs. 748/μL), but a profound deficiency of CD8+ T cells (0.79%, abs. 11/μL). In our case, genetic analysis identified a homozygous pathogenic variant in the DCLRE1C gene. The presence of an XX cell line suggested maternal T-cell engraftment. The patient underwent HSCT; however, post-transplant disseminated tuberculosis required antituberculosis therapy and significantly affected the outcome. This case underscores the importance of early diagnosis and, specifically, early antimycobacterial prophylaxis in SCID: although the diagnosis was genetically confirmed at 4 months of age, prophylactic antimycobacterial treatment was not started until disseminated BCG disease was identified 3.5 months later, at 7.5 months of age, and this delay was followed by prolonged multidrug antimycobacterial therapy and a complicated post-transplant course. This highlights the risks of administering live vaccines before immune status is confirmed and reinforces the critical role of newborn screening programs for SCID, which Latvia began implementing on April 1, 2023.

Surgical Management of Left Main Bronchus Compression Due to Pulmonary Tuberculosis in Children: The Role of Posterior Aortopexy.

Goussard Pierre P, Janson Jacques J, Eber Ernst E, Andronikou Savvas S et al.

Case Report: Analysis of antimicrobial therapy and pharmaceutical care of mixed Aspergillus and Mycobacterium tuberculosis infection following renal transplantation: a case study.

Zhang Jiao J, Zhao Yue Y, Peng Yang Y, Zheng Xin X

Invasive infection is a significant complication following renal transplantation. Due to long-term immunosuppressive therapy, renal transplant recipients are at high risk for fungal infections and tuberculosis, which are also major causes of mortality in this population. Triazole drugs, as first-line agents for invasive fungal infections, can cause fluctuations in the blood levels of immunosuppressants due to drug-drug interactions. Furthermore, the concomitant use of antituberculosis drugs further complicates the balance between maintaining immunosuppression and anti-infective therapy, often presenting a challenge to clinical decision-making. This article discusses the role of the clinical pharmacist in the treatment of a renal transplant recipient who developed concurrent pulmonary tuberculosis and aspergillus infection. By recommending initial regimens, adjusting doses during outpatient follow-ups, and assessing adverse drug reactions, the clinical pharmacist provided systematic pharmaceutical services. This collaboration assisted physicians in developing a personalized treatment plan, ultimately achieving favorable therapeutic outcomes for the patient.