A5042572033- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Advanced Breast Cancer Therapies
- Chronic Lymphocytic Leukemia Research
- Multiple Sclerosis Research Studies
- Cancer Immunotherapy and Biomarkers
- COVID-19 epidemiological studies
- Acute Ischemic Stroke Management
- Genetic factors in colorectal cancer
- T-cell and B-cell Immunology
- Adipokines, Inflammation, and Metabolic Diseases
- Immunodeficiency and Autoimmune Disorders
- Cancer-related cognitive impairment studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hematopoietic Stem Cell Transplantation
- Animal Virus Infections Studies
- Cancer Mechanisms and Therapy
- Long-Term Effects of COVID-19
- Acute Lymphoblastic Leukemia research
- Vaccine Coverage and Hesitancy
- Viral gastroenteritis research and epidemiology
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2021-2025
Technische Universität Berlin
2020-2025
Charité - Universitätsmedizin Berlin
2020-2024
University of Rostock
2020-2024
Freie Universität Berlin
2021-2023
Humboldt-Universität zu Berlin
2021-2023
Heinrich Heine University Düsseldorf
2002
The functional relevance of preexisting cross-immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a subject intense debate. Here, we show that human endemic (HCoV)–reactive and SARS-CoV-2–cross-reactive CD4+ T cells are ubiquitous but decrease with age. We identified universal immunodominant coronavirus-specific spike peptide (S816-830) demonstrate spike- S816-830–reactive were recruited into immune responses SARS-CoV-2 infection their frequency correlated...
Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly unfolding pandemic, overwhelming health care systems worldwide 1 . Clinical manifestations of Coronavirus-disease 2019 (COVID-19) vary broadly, ranging from asymptomatic infection to failure and death , yet the underlying mechanisms for this high variability are still unknown. Similarly, role host immune responses in viral clearance COVID-19 remains unresolved. For SARS-CoV (2002/03), however, it been...
Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. However, age comorbidities can compromise protection severe disease, antibody-mediated is undercut by viral immune escape mutations. Whether what extent durable T cell responses compensate for reduced humoral immunity, particularly elderly, not been investigated. Here, we utilize SARS-CoV-2-specific pan-coronavirus-derived peptide pools, including or excluding spike...
SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter vaccine immunogenicity in patients with autoimmune diseases.
Abstract Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this group. To elucidate age-related differences immunogenicity, we analyzed human cellular, serological, salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine old (69–92 y) middle-aged (24–57 vaccinees compared with natural infection (COVID-19 convalescents, 21–55 y of age). Serological humoral...
Mismatch repair-deficient (dMMR) tumors show a good response toward immune checkpoint inhibitors (ICI), but developing resistance impairs patients' outcomes. Here, we compared the therapeutic potential of an α-PD-L1 antibody with CDK4/6 inhibitor abemaciclib in two preclinical mouse models dMMR cancer, focusing on immune-modulatory effects either treatment. Abemaciclib monotherapy significantly prolonged overall survival Mlh1-/- and Msh2loxP/loxP;TgTg(Vil1-cre) mice (Mlh1-/-: 14.5 wks vs....
While evidence for pre-existing SARS-CoV-2-cross-reactive CD4 + T cells in unexposed individuals is increasing, their functional significance remains unclear. Here, we comprehensively determined SARS-CoV-2-cross-reactivity and human coronavirus-reactivity individuals. were ubiquitous, but presence decreased with age. Within the spike glycoprotein fusion domain, identified a universal immunodominant coronavirus-specific peptide epitope ( iCope ). Pre-existing spike- -reactive memory...
The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T-cells. To this end, we tracked αβT-cell clonotypes during mobilization treatment with granulocyte-colony stimulating factor (G-CSF) healthy donors for six months immune reconstitution after transfer to transplant recipients. More than 250 were from recipient. These consisted almost exclusively CD8 + effector memory T cells...
Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting proven anti-tumor activity. We herein, characterize the effect on B-ALL lines primary samples investigate potential synergistic effects BCL-2 inhibitor venetoclax to overcome limitations induction. incubation reduced phosphorylation...
Currently available COVID-19 vaccines include inactivated virus, live attenuated mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as main immunogen result in reduced disease severity upon SARS-CoV-2 infection. While we others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, effect vector this regard is unknown. Here, studied cellular humoral responses heterologous...
Abstract Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus for more durable protection is being discussed but has remained understudied. We here investigated the effects age, mutations, and homo-/heterologous vaccination regimens on dominant pan-coronavirus-specific cellular humoral epitope iCope after SARS-CoV-2 infection in detail. In older, quantitatively, qualitatively reduced iCope-reactive CD4 + T cell responses with narrow TCR...
Mlh1-knock-out-driven mismatch-repair-deficient (dMMR) tumors can be targeted immunologically. By applying therapeutic tumor vaccination, growth is delayed but escape mechanisms evolve, including upregulation of immune-checkpoint molecules (LAG-3, PD-L1). To counteract immune escape, we investigated the activity a combined vaccine-immune-checkpoint inhibitor therapy using α-PD-L1.In this trial, Mlh1-knock-out mice with established gastrointestinal received single or thrice injections α-PD-L1...
Abstract Despite extensive research on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination responses in healthy individuals, there is comparatively little known beyond antibody titers and T‐cell the vulnerable cohort of patients after allogeneic hematopoietic stem cell transplantation (ASCT). In this study, we assessed serological response performed longitudinal multimodal analyses including functionality single‐cell RNA sequencing combined with T receptor (TCR)/B (BCR)...
Abstract Thromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated effects of chemotherapeutics CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), dinaciclib (CDK1/2/5/9) alone combination regimens on TF abundance coagulation. The human colorectal (CRC) cell line HROC173 was treated with 5-FU or gemcitabine stimulate expression. + cells...
Abstract Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this group. To elucidate age-related differences immunogenicity, we analysed human cellular, serological salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine old (69-92 years) middle-aged (24-57 vaccinees compared natural infection (COVID-19 convalescents, 21-55 years). Serological humoral exceeded...
Abstract Background: Mlh1-knock-out-driven mismatch-repair-deficient (dMMR) tumors can be targeted immunologically. By applying therapeutic tumor vaccination, growth is delayed but escape mechanisms evolve, characterized by the upregulation of immune-checkpoint molecules (LAG-3, PD-L1). To counteract immune escape, we investigated activity a combined vaccine-immune checkpoint inhibitor therapy using α-PD-L1 monoclonal antibody clone 6E11.Design: In this trial, Mlh1-knock-out mice with...
Abstract SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter vaccine immunogenicity in patients with autoimmune diseases. Here we investigated the induction stability vaccine-specific antibodies, B cells, T cells multiple sclerosis (MS) different DMTs a prospective cohort study up to 6 months after homologous prime-boost vaccination. We analysed 103 MS...
The most important predictors for outcomes after ischemic stroke, that is, health deterioration and death, are chronological age stroke severity; gender, genetics environmental factors also play a role. Of all these, only the latter can be influenced event, even though recurrent may prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, treatment cardiovascular risk factors. Moreover, blood cell composition protein biomarkers such as C-reactive or interleukins...
The most important predictors for outcomes after ischemic stroke, that is, health deterioration and death, are chronological age stroke severity; gender, genetics lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced event, even though recurrent may prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, treatment cardiovascular risk factors. Moreover, blood cell composition protein biomarkers such as C-reactive or...