A5052178975- SARS-CoV-2 and COVID-19 Research
- Hepatitis Viruses Studies and Epidemiology
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Heparin-Induced Thrombocytopenia and Thrombosis
- Retinal and Optic Conditions
- Liver Disease and Transplantation
- vaccines and immunoinformatics approaches
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Hepatitis C virus research
- Viral Infections and Immunology Research
- interferon and immune responses
- Infectious Encephalopathies and Encephalitis
- Macrophage Migration Inhibitory Factor
- Cytokine Signaling Pathways and Interactions
- Veterinary medicine and infectious diseases
- Histiocytic Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Bacillus and Francisella bacterial research
- Bacteriophages and microbial interactions
University of Lübeck
2021-2025
Medizinische Hochschule Hannover
2018-2024
Abstract Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) in individuals older than 60 years, leaving millions already ChAd-primed with the decision to receive either a second shot ChAd or heterologous boost vaccines. However, such combinations have not...
RNA vaccines are efficient preventive measures to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. High levels of neutralizing SARS-CoV-2 antibodies an important component vaccine-induced immunity. Shortly after initial two mRNA vaccine doses, immunoglobulin G (IgG) response mainly consists proinflammatory subclasses IgG1 and IgG3. Here, we report that several months second vaccination, SARS-CoV-2–specific were increasingly composed noninflammatory IgG4,...
Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of lungs from viral infections. To induce those essential components lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that single MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ cells, albeit...
Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared repeated application of the same vaccine. However, data comparing decline after homologous and heterologous as well effects third ChAd/BNT are lacking. Here we show longitudinal monitoring ChAd/ChAd (n = 41) 88) vaccinated individuals impact BNT. The greatly augments waning...
Background and Aims: HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise has proven other viruses. However, precise mechanisms host factors required during unclear. Cellular proteases have emerged as surface protein activation productive cell by many Hence, we investigated functional requirement therapeutic potential cellular protease infection. Approach...
The innate and adaptive roles of γδ T cells their clonal cell receptors (TCRs) in immune responses are still unclear. Recent studies TCR repertoire dynamics showed massive expansion individual Vδ1+ clones during viral infection. To judge whether such is random or actually represents TCR-dependent responses, information about cognate ligands required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, CIITA as required for target recognition a CMV-induced Vγ3Vδ1+...
Abstract Hepatitis E virus (HEV) causes 3.3 million symptomatic cases and 44,000 deaths per year. Chronic infections can arise in immunocompromised individuals, pregnant women may suffer from fulminant disease as a consequence of HEV infection. Despite these important implications for public health, no specific antiviral treatment has been approved to date. Here, we report combined functional, biochemical, X-ray crystallographic studies that characterize the human antibody response...
During primary varicella zoster virus (VZV) infection, infected lymphocytes drive viremia, causing systemic dissemination throughout the host, including skin. This results in cytokine expression, interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to prior secondary viremia. It is not clear how achieves this while evading response. Here, we show that glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing expression of a subset...
We have used chemical shift perturbation (CSP) and saturation transfer difference (STD) NMR experiments to identify characterize the binding of selected ligands receptor-binding domain (RBD) spike glycoprotein (S-protein) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). also subjected full-length S-protein STD experiments, allowing correlations with RBD-based results. CSPs reveal sites for heparin fondaparinux, affinities were measured using CSP titrations. then show that...
ABSTRACT The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by emergence variants concern (VOCs), which have acquired mutations to escape neutralizing (nAbs). These are not evenly distributed on RBD surface but cluster several distinct surfaces, suggesting an influence targeted epitope capacity neutralize a broad range VOCs. Here, we identified potent nAb from convalescent patients Except for Lambda and BA.2.86...
ABSTRACT Cellular antiviral proteins interfere with distinct steps of replication cycles viruses. The galectin 3 binding protein (LGALS3BP, also known as 90K) was previously shown to lower the infectivity nascent human immunodeficiency virus type 1 (HIV-1) virions when expressed in virus-producing cells. This effect accompanied by impaired gp160Env processing and reduced viral incorporation mature Env glycoproteins. Here, we examined ability 90K orthologs from primate species reduce particle...
Abstract Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As consequence, several European governments recommended using this vaccine only individuals older than 60 years leaving millions of ChAd primed the decision to either receive second shot or heterologous boost mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover...
We have used NMR experiments to explore the binding of selected glycans and glycomimetics SARS CoV-2 spike glycoprotein (S-protein) its receptor domain (RBD). STD confirm sialoglycans S-protein prototypic Wuhan strain virus yield dissociation constants in millimolar range. The absence effects for presence Omicron/BA.1 reflects a loss as result evolution. Likewise, no are observed deletion mutant Δ143-145 S-protein, thus supporting localization site N-terminal (NTD). Oseltamivir Zanamivir...
Abstract Cerebral venous thrombosis was reported as a rare but serious adverse event in young and middle-aged vaccinees following immunization with AstraZeneca’s ChAdOx1-nCov-19 vaccine. As consequence, several European governments recommended using this vaccine only individuals older than 60 years leaving millions of ChAd primed the decision to either receive second shot or heterologous boost mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover...
Abstract During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T particular, causes viremia allowing systemic spread throughout host, including skin. This results expression cytokines, interferons (IFNs) which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior secondary viremia. How while evading cytokine response has not been fully established....
Abstract Repeated mRNA vaccinations are an efficient tool to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies important component vaccine-induced immunity. Shortly after first or second vaccine dose, IgG response mainly consists pro-inflammatory isotypes IgG1 and IgG3 is driven by T helper (Th) 1 cells. Here, we report that several months vaccination, SARS-CoV-2-specific antibodies were increasingly composed non-inflammatory IgG2 particularly IgG4, which...
Kaposi Sarcoma-associated herpesvirus (KSHV) causes three human malignancies, Sarcoma (KS), Primary Effusion Lymphoma (PEL) and the plasma cell variant of multicentric Castleman’s Disease (MCD), as well an inflammatory cytokine syndrome (KICS). Its non-structural membrane protein, pK15, is among a limited set viral proteins expressed in KSHV-infected KS tumor cells. Following its phosphorylation by Src family tyrosine kinases, pK15 recruits phospholipase C gamma 1 (PLCγ1) to activate...
Abstract Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA (e.g. BNT162b2, BNT) appeared be superior in inducing protective immunity, and large scale second booster ongoing. However, data comparing declining immunity after homologous heterologous as well effects third application...
Abstract Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA (e.g. BNT162b2, BNT) appeared be superior in inducing protective immunity, and large scale second booster ongoing. However, data comparing declining immunity after homologous heterologous as well effects third application...
Hepatitis E virus (HEV) is a non-enveloped single-stranded RNA and the most common cause of acute hepatitis in humans worldwide. Serological marker studies showed that 420.000 individuals Germany become infected with HEV annually. Chronic infections can arise approximately 50% immunosuppressed individuals. This lead to rapid progression liver fibrosis cirrhosis ultimate need for transplantation. As no approved treatment currently available, there an urgent effective antiviral therapeutics.
Although infection with the Hepatitis E Virus (HEV) is most common cause of acute viral hepatitis worldwide, serological response in HEV infected patients not yet fully understood. Interestingly, immunocompromised individuals are often unable to clear virus and develop chronic infection. During infection, high amounts glycosylated non-infectious dimers HEV’s capsid protein (pORF2) secreted. These can be found serum even after clearance as determined by undetected HEV-RNA stool serum. We...