A5015543699- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Respiratory viral infections research
- Biochemical and Molecular Research
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- RNA Interference and Gene Delivery
- Chemical Reactions and Isotopes
- Advanced biosensing and bioanalysis techniques
- Mosquito-borne diseases and control
- Radiation Effects and Dosimetry
- Viral gastroenteritis research and epidemiology
- Microbial Inactivation Methods
- Pneumonia and Respiratory Infections
- Virology and Viral Diseases
- Monoclonal and Polyclonal Antibodies Research
- Neonatal Respiratory Health Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Metabolism and Genetic Disorders
- SARS-CoV-2 detection and testing
- Viral Infections and Vectors
- Enzyme Structure and Function
- Photovoltaic Systems and Sustainability
- Fluorine in Organic Chemistry
- Insect and Pesticide Research
Fraunhofer Institute for Cell Therapy and Immunology
2019-2024
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...
The nucleoside analog N4-hydroxycytidine (NHC) is the active metabolite of prodrug molnupiravir, which has been approved for treatment COVID-19. SARS-CoV-2 incorporates NHC into its RNA, resulting in defective virus genomes. Likewise, inhibitors dihydroorotate dehydrogenase (DHODH) reduce yield upon infection, by suppressing cellular synthesis pyrimidines. Here, we show that and DHODH strongly synergize inhibition replication vitro. We propose lack available pyrimidine nucleotides increases...
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...
Abstract New strategies for the rapid development of broad‐spectrum antiviral therapies are urgently required emerging and re‐emerging viruses like severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Host‐directed antivirals that target universal cellular metabolic pathways necessary viral replication present a promising approach with activity low potential resistance. Dihydroorotate dehydrogenase (DHODH) was identified as one those host factors essential many clinically relevant...
Inhibitors of viral cell entry based on poly(styrene sulfonate) and its core-shell nanoformulations gold nanoparticles are investigated against a panel viruses, including clinical isolates SARS-CoV-2. Macromolecular inhibitors shown to exhibit the highly sought-after broad-spectrum antiviral activity, which covers most analyzed enveloped viruses all variants concern for SARS-CoV-2 tested. The inhibitory activity is quantified in vitro appropriate culture models respiratory pathogens...
Ionizing radiation is widely used to inactivate pathogens. It mainly acts by destroying nucleic acids but causes less damage structural components like proteins. therefore highly suited for the sterilization of biological samples or generation inactivated vaccines. However, inactivation viruses bacteria requires relatively high doses and substantial amounts energy. Consequently, irradiation restricted shielded facilities-protecting personnel environment. We have previously shown that low...
Human respiratory syncytial virus (RSV) is the leading cause of severe lower tract infections in infants, elderly, and immunocompromised, yet no licensed vaccine only limited therapeutic options for prevention treatment are available, which poses a global health challenge emphasizes urgent medical need novel antiviral agents. In current study, potent small molecule inhibitor RSV was identified by performing screening structure optimization campaign, wherein naturally occurring...
Despite tremendous global efforts since the beginning of COVID-19 pandemic, still only a limited number prophylactic and therapeutic options are available. Although vaccination is most effective measure in preventing morbidity mortality, there need for safe post-infection treatment medication. In this study, we explored pipeline 21 potential candidates, examined Calu-3 cell line their antiviral efficacy, drug repurposing. Ralimetinib nafamostat, clinically used drugs, have emerged as...
The respiratory syncytial virus (RSV) is one major cause of lower tract infections in childhood and an effective vaccine still not available. We previously described a new rhabdoviral vector vaccine, VSV-GP, variant the vesicular stomatitis (VSV), where VSV glycoprotein G exchanged by GP lymphocytic choriomeningitis virus. Here, we evaluated VSV-GP as for RSV with aim to induce neutralizing antibodies. Wild-type F (Fwt) or codon optimized version (Fsyn) were introduced at position 5 into...
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 COVID-19 pandemic caused by SARS-CoV-2 presents a global health emergency. Therapeutic options against are still very limited but urgently required. Molecular tweezers supramolecular agents that destabilize the envelope of viruses resulting in loss viral infectivity. Here, we show first-generation tweezers, CLR01 and CLR05, disrupt abrogate To increase antiviral activity, series 34 advanced molecular were synthesized insertion aliphatic or aromatic ester groups on phosphate moieties...
Introduction West Nile Virus (WNV) is a zoonotic flavivirus transmitted by mosquitoes. Especially in the elderly or immunocompromised individuals an infection with WNV can lead to severe neurological symptoms. To date, no human vaccine against available. The Envelope (E) protein, located at surface of flaviviruses, involved invasion into host cells and major target for neutralizing antibodies therefore central development. Due their close genetic structural relationship, flaviviruses share...
Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus which endemic in many European and Asian countries. Humans can get infected with TBEV usually via ticks, possible symptoms of the infection range from fever to severe neurological complications such as encephalitis. Vaccines protect against TBEV-induced disease are widely used most them consist whole viruses, inactivated by formaldehyde. Although this production process well established, it has several drawbacks, including usage...
Human respiratory syncytial virus (RSV) is the primary cause of acute lower tract infections in children and elderly worldwide, for which neither a vaccine nor an effective therapy approved. The entry RSV into host cell mediated by stepwise structural changes surface fusion (RSV-F) glycoprotein. Recent progress functional studies RSV-F glycoprotein revealed conformation-dependent neutralizing epitopes have become attractive targets therapeutic development. As present on viral trimeric form,...
SARS-CoV-2 incorporates the nucleoside analogue N4-hydroxycytidine (NHC) into its RNA through RNA-dependent polymerase (RdRp). NHC is active metabolite of prodrug Molnupiravir (MK-4482), which has recently been approved in United Kingdom (UK) for treatment COVID-19. Likewise, inhibitors dihydroorotate dehydrogenase (DHODH), by reducing cellular synthesis pyrimidines, also reduce virus yield upon infection. Here we show that and DHODH strongly synergize inhibition replication. While single...
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.
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...
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...