Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients.

Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of making and safely utilizing such virus-specific T cells clinically was assessed by administering partially HLA-matched, third-party, cryopreserved SARS-CoV-2-specific T cells (ALVR109) in combination with other antiviral agents to four individuals who were hospitalized with COVID-19. This study establishes the feasibility of preparing and delivering off-the-shelf, SARS-CoV-2-directed, virus-specific T cells to patients with COVID-19 and supports the clinical use of these products outside of the profoundly immune compromised setting (ClinicalTrials.gov number, NCT04401410).

Borrelia miyamotoi Meningoencephalitis in an Immunocompetent Patient.

Borrelia miyamotoi is an underdiagnosed cause of tick-borne illness in endemic regions and, in rare cases, causes neurological disease in immunocompetent patients. Here, we present a case of serologically confirmed Borrelia miyamotoi meningoencephalitis in an otherwise healthy patient who rapidly improved following initiation of antibiotic therapy.

Evaluation of cyclin A1-specific T cells as a potential treatment for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for relapsed or refractory acute myeloid leukemia (AML). However, more than half ultimately experience disease relapse that is associated with a dismal median survival of just 6 months, highlighting the need for novel therapies. In the current study we explore the therapeutic potential of targeting cyclin A1 (CCNA1), a cancer-testis antigen that is overexpressed in malignant blasts and leukemic stem cells. We demonstrate the immunogenicity of this antigen to native T cells, with >90% of donors screened mounting a specific response. The expanded cells were Th1 polarized, polyfunctional, and cytotoxic toward CCNA1+/HLA-matched tumor cell lines. Furthermore, these cells were exquisitely specific for CCNA1 and exhibited no reactivity against other cyclin family members, including CCNA2, which shares 56% homology with CCNA1 and is ubiquitously expressed in dividing cells. Lastly, the detection of CCNA1-specific T cells in AML patients post-HSCT was associated with prolonged disease remission, suggesting the protective potential of such endogenous cells. Taken together, our findings demonstrate the feasibility of targeting CCNA1 and the potential for therapeutic benefit associated with the adoptive transfer of reactive cells.

A systematic analysis on prevalence and sub-regional distribution of undiagnosed diabetes mellitus among adults in African countries.

BACKGROUND: Despite the high prevalence of diabetes in Africa, the extent of undiagnosed diabetes in the region is still poorly understood. This systematic review and meta-analysis was designed to determine the pooled prevalence of undiagnosed diabetes mellitus among adults in Africa. METHODS: We conducted a systematic desk review and electronic web-based search of PubMed, Google Scholar, EMBASE, and the World Health Organization's Hinari portal (which includes the SCOPUS, African Index Medicus, and African Journals Online databases), identifying peer-reviewed research studies on the prevalence of undiagnosed diabetes among adult individuals using pre-defined quality and inclusion criteria. We ran our search from June 1, 2018 to Jun 14, 2020. We extracted relevant data and presented descriptive summaries of the studies in tabular form. The I2 test was used to assess heterogeneity across studies. A random effects model was used to estimate the pooled prevalence of undiagnosed diabetes mellitus at a 95% confidence interval (CI). Funnel plot asymmetry and Egger's tests were used to check for publication bias. The final effect size was determined by applying a trim and fill analysis in a random-effects model. RESULTS: Our search identified 1442 studies amongst which 23 articles were eligible for inclusion in the final meta-analysis. The average pooled prevalence of undiagnosed diabetes mellitus among adults was 3.85 (95% CI: 3.10-4.60). The pooled prevalence of undiagnosed diabetes mellitus based on geographic location was 4.43 (95% CI: 3.12-5.74) in Eastern Africa; 4.72 (95% CI: 2.64-6.80) in Western Africa; 4.27 (95% CI: 1.77-6.76) in Northern Africa and 1.46 (95%CI: 0.57-2.34) in southern Africa respectively. CONCLUSION: Our findings indicate a high prevalence of undiagnosed diabetes in Africa and suggest that it may be more prevalent in Western Africa than the rest of the regions. Given the high levels of undiagnosed diabetes in the Africa region, more attention should be paid to incorporating diabetes screening and treatment services into existing diabetes related programs to reduce the prevalence of undiagnosed cases.