https://repository.seku.ac.ke/handle/123456789/1817 2026-04-04T15:00:50Z 2026-04-04T15:00:50Z Mbogori, Elius Musyoki, Stanslaus K. Biegon, Richard Patel, Kirtika https://repository.seku.ac.ke/handle/123456789/8281 2026-03-09T11:46:38Z 2025-06-01T00:00:00Z

Title: Bioinformatic identification of conserved epitopes from SARS-COV-2 genome isolated in Kenya Authors: Mbogori, Elius; Musyoki, Stanslaus K.; Biegon, Richard; Patel, Kirtika Abstract: The development of vaccines and diagnostic tools for SARS-CoV-2 heavily relies on identifying conserved epitopes across various virus strains. BLASTp is a pivotal bioinformatics tool for comparing protein sequences to unveil regions of similarity, aiding in understanding evolutionary relationships and functional conservation. The current study used bioinformatics methods to highlight the conserved epitopes on SARS-CoV-2 genomes isolated in Moi Teaching and Referral Hospital. To achieve this objective, the genomes were divided into their constituent genes using NCBI ORFfinder and translated to proteins using EXPASY. BlastP was then used to identify the proteins. Meanwhile, epitopes from the Wuhan genome were downloaded from IEDB and a BlastP analysis was done to identify matching epitopes. From the IEDB databank, 12,285 Wuhan genome epitopes were found and on conducting BlastP analysis, 5154 epitopes were isolated. These epitopes were deemed conserved as they had not changed despite numerous mutations. The identification and analysis of the conserved epitopes in the SARS-CoV-2 genome are crucial for the development of effective vaccines and diagnostic tools. Further laboratory experiments are however recommended to ascertain them to be conserved epitopes. Description: https://doi.org/10.1016/j.nexres.2025.100215

2025-06-01T00:00:00Z Sang, Jenniffer C. Musyoki, Stanslaus K. Injera, Wilfred E. Karani, Lucy W. Maiyoh, Geoffrey K. https://repository.seku.ac.ke/handle/123456789/8278 2026-03-09T08:41:42Z 2025-06-01T00:00:00Z

Title: Cytokine immune profiles among COVID 19 patients with different disease severities seeking treatment at Moi teaching and referral hospital, Kenya Authors: Sang, Jenniffer C.; Musyoki, Stanslaus K.; Injera, Wilfred E.; Karani, Lucy W.; Maiyoh, Geoffrey K. Abstract: Background COVID-19 manifests with a wide range of severities, from asymptomatic to critical conditions. Immunological profiles in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may serve as early indicators of disease severity, aiding in prioritizing patient care. Methodology Archived patient plasma samples were retrieved from the Molecular Lab Bio-repository, ensuring equal representation of males, females, and various disease severities. Socio-demographic and disease severity data were obtained from patient health records. Levels of pro-inflammatory cytokines (interferon-gamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], interleukin-2 [IL-2], and interleukin-17 [IL-17]) and anti-inflammatory cytokines (interleukin-4 [IL-4], interleukin-6 [IL-6], and interleukin-10 [IL-10]) were measured using the BD FACSCalibur flow cytometer. Data analysis involved comparing cytokine levels across different disease severities, with demographic data expressed as means ± standard deviation (SD). Statistical significance was set at P ≤ 0.05. Findings The mean ages for males and females were 49.6 ± 22.7 and 48.4 ± 23.7, respectively. Mean ages for disease severity categories were 33 ± 19 (asymptomatic), 45.2 ± 21.5 (moderate), 56.8 ± 18.7 (severe), and 61.95 ± 22 (critical). Comorbidities were present in 25 % of patients, with cardiovascular disease (41 %) and pulmonary disease (31 %) being the most common. Predominant symptoms in critical patients included dyspnea (63 %) and myalgia (60 %), while rhinorrhea (46.2 %) and chest pain (45.7 %) were common in severe cases. Gastrointestinal symptoms were observed only in severe and critical groups. Levels of the pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-17) increased linearly with disease severity. Among anti-inflammatory cytokines, IL-6 and IL-10 levels also rose significantly with increasing severity. Conclusion Levels of TNF-α, IL-17, and IL-6 correlated with disease severity and may serve as prognostic biomarkers. Advanced age and underlying comorbidities were independently associated with higher disease severity. Description: https://doi.org/10.1016/j.cyto.2025.156917

2025-06-01T00:00:00Z Laubert, Miriam Bonifacius, Agnes Dragon, Anna C. Mangare, Caroline Blasczyk, Rainer Huehn, Jochen Eiz-Vesper, Britta https://repository.seku.ac.ke/handle/123456789/8264 2026-02-17T08:02:07Z 2022-03-30T00:00:00Z

Title: Enhancement of antiviral t-cell responses by vitamin c suggests new strategies to improve manufacturing of virus-specific t cells for adoptive immunotherapy Authors: Laubert, Miriam; Bonifacius, Agnes; Dragon, Anna C.; Mangare, Caroline; Blasczyk, Rainer; Huehn, Jochen; Eiz-Vesper, Britta Abstract: Allogeneic and autologous transplantation of hematopoietic stem cells (HSCT) are being routinely used to treat patients with leukemia and lymphoma. Due to the required immunosuppression after stem cell transplantation, infection and reactivation by viruses are life-threatening complications. In recent years, adoptive transfer using virus-specific T cells (VSTs) has emerged as alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate VST function and thereby enable an improvement of therapy. For that, we investigated the impact of vitamin C and D on the functionality of cytomegalovirus (CMV)-specific T cells isolated from CMV-seropositive healthy donors. We were able to show that vitamin C increases the expansion and activation state of CMV-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. A higher frequency of the terminally differentiated effector memory CD8+ T-cell population in these donors indicates a connection between these cells and the enhanced response to vitamin C. Thus, here we provide insights into the impact of vitamin C on cytotoxic T cells as well as possible additional selection criteria and strategies to improve VST functionality Description: doi: 10.3390/biology11040536

2022-03-30T00:00:00Z Dragon, Anna C. Zimmermann, Katharina Nerreter, Thomas Sandfort, Deborah Lahrberg, Julia Klöß, Stephan Kloth, Christina Mangare, Caroline Bonifacius, Agnes Tischer-Zimmermann, Sabine Blasczyk, Rainer Maecker-Kolhoff, Britta Uchanska-Ziegler, Barbara Abken, Hinrich Schambach, Axel Hudecek, Michael Eiz-Vesper, Britta https://repository.seku.ac.ke/handle/123456789/8263 2026-02-17T07:33:59Z 2020-01-01T00:00:00Z

Title: CAR-T cells and TRUCKs that recognize an EBNA-3C-derived epitope presented on HLA-B*35 control pstein-barr virus-associated lymphoproliferation Authors: Dragon, Anna C.; Zimmermann, Katharina; Nerreter, Thomas; Sandfort, Deborah; Lahrberg, Julia; Klöß, Stephan; Kloth, Christina; Mangare, Caroline; Bonifacius, Agnes; Tischer-Zimmermann, Sabine; Blasczyk, Rainer; Maecker-Kolhoff, Britta; Uchanska-Ziegler, Barbara; Abken, Hinrich; Schambach, Axel; Hudecek, Michael; Eiz-Vesper, Britta Abstract: Background Immunosuppressive therapy or T-cell depletion in transplant patients can cause uncontrolled growth of Epstein-Barr virus (EBV)-infected B cells resulting in post-transplant lymphoproliferative disease (PTLD). Current treatment options do not distinguish between healthy and malignant B cells and are thereby often limited by severe side effects in the already immunocompromised patients. To specifically target EBVinfected B cells, we developed a novel peptide-selective chimeric antigen receptor (CAR) based on the monoclonal antibody TÜ165 which recognizes an Epstein-Barr nuclear antigen (EBNA)−3C-derived peptide in HLA-B*35 context in a T-cell receptor (TCR)-like manner. In order to attract additional immune cells to proximity of PTLD cells, based on the TÜ165 CAR, we moreover generated T cells redirected for universal cytokine-mediated killing (TRUCKs), which induce interleukin (IL)-12 release on target contact. Methods TÜ165-based CAR-T cells (CAR-Ts) and TRUCKs with inducible IL-12 expression in an all-in-one construct were generated. Functionality of the engineered cells was assessed in co-cultures with EBNA-3C-peptide-loaded, HLA-B*35-expressing K562 cells and EBV-infected B cells as PTLD model. IL-12, secreted by TRUCKs on target contact, was further tested for its chemoattractive and activating potential towards monocytes and natural killer (NK) cells. Results After co-cultivation with EBV target cells, TÜ165 CAR-Ts and TRUCKs showed an increased activation marker expression (CD137, CD25) and release of proinflammatory cytokines (interferon-γ and tumor necrosis factor-α). Moreover, TÜ165 CAR-Ts and TRUCKs released apoptosis-inducing mediators (granzyme B and perforin) and were capable to specifically lyse EBV-positive target cells. Live cell imaging revealed a specific attraction of TÜ165 CAR-Ts around EBNA-3C-peptide-loaded target cells. Of note, TÜ165 TRUCKs with inducible IL-12 showed highly improved effector functions and additionally led to recruitment of monocyte and NK cell lines. Conclusions Our results demonstrate that TÜ165 CARTs recognize EBV peptide/HLA complexes in a TCR-like manner and thereby allow for recognizing an intracellular EBV target. TÜ165 TRUCKs equipped with inducible IL-12 expression responded even more effectively and released IL-12 recruited additional immune cells which are generally missing in proximity of lymphoproliferation in immunocompromised PTLD patients. This suggests a new and promising strategy to specifically target EBV-infected cells while sparing and mobilizing healthy immune cells and thereby enable control of EBV-associated lymphoproliferation. Description: doi:10.1136/jitc-2020-000736

2020-01-01T00:00:00Z