A5021635776- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- Neonatal Health and Biochemistry
- Prostate Cancer Diagnosis and Treatment
- HIV Research and Treatment
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Prostate Cancer Treatment and Research
- Viral Infections and Outbreaks Research
- Respiratory viral infections research
- Advanced biosensing and bioanalysis techniques
Friedrich-Alexander-Universität Erlangen-Nürnberg
2020-2024
Universitätsklinikum Erlangen
2020-2024
Leipzig University
2024
1928 Diagnostics (Sweden)
1999
Several effective SARS-CoV-2 vaccines are currently in use, but boosters needed to maintain or increase immunity due waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 19a vectored following a systemic plasmid DNA mRNA priming result mucosal mice. In contrast two intramuscular applications an vaccine, boosts adenoviral vectors induce high levels IgA lung-resident memory T cells (TRM); neutralization virus variants concern is...
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,...
The ongoing pandemic coronavirus (CoV) disease 2019 (COVID-19) by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has already caused substantial morbidity, mortality, and economic devastation. Reverse genetic approaches to generate recombinant viruses are a powerful tool characterize understand newly emerging viruses. To contribute the global efforts for countermeasures control spread of SARS-CoV-2, we developed passage-free SARS-CoV-2 clone based on bacterial artificial chromosome...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on complementation of GFP and luciferase to quantify fusogenic activity SARS-CoV-2 spike protein. provide several lines evidence that SARS-CoV-2, but not SARS-CoV-1, induced cell–cell fusion even in absence receptor,...
The ongoing pandemic spread of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) demands skillful strategies for novel drug development, repurposing and cotreatments, in particular focusing on existing candidates host-directed antivirals (HDAs). developmental IMU-838, currently being investigated a phase 2b trial patients suffering from autoimmune diseases, represents an inhibitor human dihydroorotate dehydrogenase (DHODH) with recently proven antiviral activity vitro...
Abstract SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing serious pandemic. While reliable nucleic acid–based diagnostic assays were rapidly available, only limited number of validated serological available in the early phase Here, we evaluated novel flow cytometric approach to assess spike-specific antibody responses.HEK 293T cells expressing spike protein its natural confirmation on surface used detect specific IgG and IgM responses patient...
Twelve research groups participated in the ISOBM TD-3 Workshop which reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays immunohistochemistry, categorized into six major formed basis for mapping onto two- three-dimensional (2-D 3-D) models PSA. The overall findings are summarized this report. In agreement with all participating...
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate monoclonal antibodies. After immunizing these with DNA encoding the spike protein SARS-CoV-2 boosting protein, we identified 29 hybridoma antibodies that reacted protein. Nine neutralize infection at IC50 values in subnanomolar range. ELISA-binding studies sequence analyses revealed one cluster three clonally related neutralizing target receptor-binding domain compete...
The assessment of SARS-CoV-2 infections in children is still challenging, but essential for appropriate political decisions. aim this study was to investigate whether residual blood samples can be used seroprevalence monitoring pediatrics.In repeated cross-sectional cohort study, anonymous from pediatric patients aged 0-17 years were collected three time-periods (Oct.-Nov. 2020, April 2021, and June-July 2021) analyzed Spike protein (anti-S) nucleocapsid (anti-N) antibodies using commercial...
To assess vaccine immunogenicity in non-infected and previously infected individuals a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, Spikevax had median neutralizing titers ranging from ID50 = 25 to 75. Individuals two immunizations Comirnaty higher ID50s...
ABSTRACT The potency of antibody neutralization in cell culture has been used as the key criterion for selection antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical development. As other aspects may also influence degree protection vivo , we compared efficacy two neutralizing monoclonal (TRES6 and 4C12) targeting different epitopes receptor binding domain (RBD) SARS-CoV-2 a prophylactic setting rhesus monkeys. All four animals treated with TRES6 had...
Mutations in the spike protein of SARS-CoV-2 can lead to evasion from neutralizing antibodies and affect efficacy passive active immunization strategies. Immunization mice harboring an entire set human immunoglobulin variable region gene segments allowed identify nine monoclonal antibodies, which either belong a cluster clonally related RBD or NTD binding antibodies. To better understand genetic barrier emergence variants resistant these escape mutants were selected cell culture one antibody...
The importance of a balanced TH1/TH2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated control is increasingly recognized. However, there no defined vaccination strategy to raise it. Since checkpoints are involved in induction adoptive immunity and their inhibitors (monoclonal antibodies) licensed cancer therapy, we investigated effect checkpoint blockade after genetic on enhancement modulation antiviral antibody responses. By intraperitoneal...
ABSTRACT TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly generate monoclonal antibodies. After immunizing these against the spike protein SARS-CoV-2, we identified 29 hybridoma antibodies that reacted with SARS-CoV-2 protein. Nine neutralized infection at IC50 values in subnanomolar range. ELISA-binding studies DNA sequence analyses revealed one cluster clonally related neutralizing target receptor-binding domain compete...
The induction of a potent and long-lasting, broadly neutralizing antibody response is one the most promising approaches in HIV-1 vaccination. Recently, we demonstrated that Gag-specific T helper cells induced by DNA priming can enhance modulate HIV Env-specific B cell upon virus-like particle (VLP) boost intrastructural help (ISH). In order to minimize potentially harmful specific TH cells, explored possibility harness heterologous recombinant tuberculosis subunit vaccine H1, which contains...
Due to the low efficacy and need for seasonal adaptation of currently licensed influenza A vaccines, importance alternative vaccination strategies is increasingly recognized. Considering that DNA vaccines can be rapidly manufactured readily adapted with novel antigen sequences, genetic a promising immunization platform. However, applicability different adjuvants this approach still represents complex challenge. Immune checkpoints are class molecules involved in adaptive immune responses...
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...
Long-acting passive immunization strategies are needed to protect immunosuppressed vulnerable groups from infectious diseases. To further explore this concept for COVID-19, we constructed Adeno-associated viral (AAV) vectors encoding the human variable regions of SARS-CoV-2 neutralizing antibody, TRES6, fused murine constant regions. An optimized vector construct was packaged in hepatotropic (AAV8) or myotropic (AAVMYO) AAV capsids and injected intravenously into syngeneic TRIANNI-mice. The...
Licensed SARS-CoV-2 vaccines induce robust systemic immune responses, but mucosal immunity in the respiratory tract form of secretory immunoglobulin A (IgA) or tissue-resident memory T cells (TRM) is not established. Inducing such front-line by boosting might reduce individual risk breakthrough infections and thereby likely mitigate infection dynamics on population level as well. The following project evaluates preclinical licensed adenoviral vector (Ad) platforms boosters.
Abstract Several effective SARS-CoV-2 vaccines are currently in use, but the light of waning immunity and emergence novel variants, boost modalities needed order to maintain or even increase immunity. Here we report that intranasal vaccinations with adenovirus 5 19a vectored following a systemic DNA mRNA priming result strong mucosal mice. In contrast two intramuscular injections an vaccine, adenoviral vectors induced high levels IgA tissue-resident memory T cells respiratory tract. Mucosal...
Live-attenuated SARS-CoV-2 vaccines present themselves as a promising approach for the induction of broad mucosal immunity. However, initial safety assessment in clinical trials, virus production requires conditions meeting Good Manufacturing Practice (GMP) standards while maintaining biosafety level 3 (BSL-3) requirements. Since facilities providing necessary complex ventilation systems to meet both requirements are rare, we here describe possibility reproducibly propagate automated, closed...