Bobosha, K. | Search bioRxiv

bioRxiv2024

Immunopeptidomics informs discovery and delivery of Mycobacterium tuberculosis MHC-II antigens for vaccine design

No currently licensed vaccine reliably prevents pulmonary tuberculosis (TB), a leading cause of infectious disease mortality. Developing effective new vaccines will require identifying which of the roughly 4000 proteins in the Mycobacterium tuberculosis (Mtb) proteome are presented on MHC class II (MHC-II) by infected human phagocytes and can be recognized by CD4+ T cells to mediate protective immunity. Vaccines must also elicit T cell responses recognizing the same peptide-MHC complexes presented by infected cells, and successful presentation of target human MHC-II peptides is currently challenging to evaluate and optimize. Here, we define antigenic targets for TB vaccine development by using mass spectrometry (MS) for proteome-wide discovery of Mtb epitopes presented on MHC-II by infected human cells. We next iteratively design and evaluate candidate mRNA vaccine immunogens, revealing design principles that enhance presentation of target MHC-II peptides. Our results will inform the development of new TB vaccine candidates.

microbiology↗

bioRxiv2024

Rare Variable M. tuberculosis Antigens induce predominant Th17 responses in human infection

CD4 T cells are essential for immunity to M. tuberculosis (Mtb), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity to Mtb. While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that as in other pathogens, effective immune recognition drives sequence diversity in individual Mtb antigens. We previously identified Mtb genes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in two distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoR{gamma}t and produce IL-17, in contrast to classical Mtb antigens that induce T cells that produce IFN{gamma}. Our results suggest that RVMA can be valuable antigens in vaccines for those already infected with Mtb to amplify existing antigen-specific Th17 responses to prevent TB disease.

immunology↗

bioRxiv2018

Knowledge and self-care practice of leprosy patients at ALERT Hospital, Ethiopia

BackgroundLeprosy is a chronic infectious disease of public health importance and one of the leading causes of permanent physical disability. The integration of leprosy service to the general health system in Ethiopia made leprosy patients to be seen by non-leprosy specialists which could lead to misdiagnosis and delay in treatment. In addition to the multi-drug treatment, patient self - care practice is crucial for the successful treatment of the disease. This study was aimed to assess the knowledge and self-care practices of leprosy patients and associated factors at ALERT leprosy referral Hospital in Ethiopia.\n\nMethodA cross-sectional study was conducted ALERT leprosy referral Hospital, Addis Ababa, Ethiopia. A total of 424 leprosy patients were interviewed using pre-tested structured questionnaires. The questionnaires included core points such as socio-demographic characteristics, knowledge of leprosy and self-care practices. Blooms cut off point was used to describe the knowledge and self-care practice of the respondents and statistical significance was assessed at 95% confidence interval with 5% of level of significance.\n\nResultThe knowledge score of the respondents was poor for 276 (65.1%) and good for 148 (34.9%). The level of knowledge was significantly varied within age groups (P= 000), sex (P=000), marital status (p=0.003), educational status (p=000) and income (p-000). More than three-fourth (77.4%) of interviewed patients had poor self-care practice and only less than a quarter (22.6%) of patients had good self-care practice score (P=000). Age (p=0.002), Previous disability due to leprosy (P=000), Knowledge of leprosy (p=0.038) and income (P=0.028) significantly associated with poor self-care practice. On the other hand, educational status, sex, marital status and health education did not associated with leprosy self-care practice.\n\nConclusionAlthough, leprosy treatment, disability prevention and rehabilitation program run in the country under general public health care service for decades, poor leprosy self-care practice and poor leprosy knowledge had been confirmed in this study. Therefore, the leprosy service program should re-visit its strategy and mode of delivery to improve the leprosy knowledge and leprosy self-care practices of patients.\n\nAuthor summaryLeprosy is an infectious bacterial disease. It is a curable disease if treated early before disability occurs with the correct regimen. However, treatment cannot reverse disability once occurred. in addition to chemotherapeutic treatment, lack of social and psychological treatment may expose patients to disability as they may not adhere to treatment. To prevent disability it is vital to empower leprosy patients through promoting self-confidence, providing knowledge and self-care skills. In the present study, we investigated the knowledge and self-care practice of 424 leprosy patients at ALERT hospital through face-to face guided interview. It was found that majority of patients had poor knowledge about leprosy. Some factors such as sex, income status, age and educational status of the patient significantly affected the level of leprosy knowledge. Similarly, it was found that 77% of patients had poor self-care practice which significantly varied with income status, knowledge of leprosy, age and having previous disability. Therefore, it is very important to improve the leprosy knowledge and self-care skills of patients. This can be achieved through dealing with issues such as the physical, emotional, intellectual and social aspects of the patients in addition to the chemotherapeutic treatment.

epidemiology↗