Biology subjects

Wirblich, C.

Publications and source records attributed to Wirblich, C..

4 recordsLinked to original sources

bioRxiv2024

A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson's Disease

In Parkinsons disease (PD), dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability. However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype of Sox6+ DANs, Anxa1+, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice. We generated a knock-in Cre mouse line for Anxa1+ DANs and showed differential anatomical inputs and outputs of this population. Further, we found that the inhibition of transmitter release in Anxa1+ neurons led to bradykinesia and tremor. Therefore, Anxa1+ is not only a biomarker of a selectively vulnerable subtype of DANs, but is also sufficient to drive early motor symptoms in Parkinsons disease.

neuroscience↗

bioRxiv2021

A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

The development of effective countermeasures against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal model of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

immunology↗

bioRxiv2021

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

microbiology↗

bioRxiv2020

Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract in the mouse model of ZIKA.

Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.

microbiology↗