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117
result(s) for
"de Wit, Emmie"
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Effectiveness of N95 Respirator Decontamination and Reuse against SARS-CoV-2 Virus
by
van Doremalen, Neeltje
,
Fischer, Robert J
,
Munster, Vincent J
in
Betacoronavirus
,
Coronavirus Infections - prevention & control
,
Coronavirus Infections - virology
2020
The coronavirus pandemic has created worldwide shortages of N95 respirators. We analyzed 4 decontamination methods for effectiveness in deactivating severe acute respiratory syndrome coronavirus 2 virus and effect on respirator function. Our results indicate that N95 respirators can be decontaminated and reused, but the integrity of respirator fit and seal must be maintained.
Journal Article
Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques
by
Benecke, Arndt G.
,
Feldmann, Heinz
,
Falzarano, Darryl
in
animal disease models
,
Animal diseases
,
Animals
2013
In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 10 ⁶ 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.
Journal Article
Next-generation vaccine platforms for COVID-19
2020
Consensus among experts is that only an effective COVID-19 vaccine will end the pandemic. This Comment focuses on how this pandemic has accelerated the development of vaccine platforms distinct from classical vaccines; these novel platforms may also increase the response time when new viruses emerge in the future.
Journal Article
ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7
by
Port, Julia R.
,
van Doremalen, Neeltje
,
Holbrook, Myndi G.
in
631/250/590
,
631/326/421
,
631/326/590/1867
2021
We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.
Emerging SARS-CoV-2 variants raise concerns about vaccine effectiveness. Here, the authors show that the ChAdOx1 nCoV-19 (AZD1222) vaccine protects Syrian hamsters from pulmonary infection and disease after infection with SARS-CoV-2 B.1.351 or B.1.1.7 variants.
Journal Article
H5N1 Virus Attachment to Lower Respiratory Tract
by
Riel, Debby van
,
Osterhaus, Ab D. M. E
,
Rimmelzwaan, Guus F
in
Animal models
,
Animals
,
Avian flu
2006
Highly pathogenic avian influenza virus (H5N1) may cause severe lower respiratory tract (LRT) disease in humans. However, the LRT cells to which the virus attaches are unknown for both humans and other mammals. We show here that H5N1 virus attached predominantly to type II pneumocytes, alveolar macrophages, and nonciliated bronchiolar cells in the human LRT, and this pattern was most closely mirrored in cat and ferret tissues. These findings may explain, at least in part, the localization and severity of H5N1 viral pneumonia in humans. They also identify the cat and the ferret as suitable experimental animals based on this criterion.
Journal Article
A Novel Coronavirus Emerging in China — Key Questions for Impact Assessment
by
van Riel, Debby
,
van Doremalen, Neeltje
,
Koopmans, Marion
in
Betacoronavirus - pathogenicity
,
China - epidemiology
,
Communicable Disease Control
2020
A novel coronavirus, designated as 2019-nCoV, emerged in Wuhan, China, at the end of 2019. Although many details of the emergence of this virus remain unknown, it has put global public health institutions on high alert.
Journal Article
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
by
Jordan, Robert
,
Feldmann, Heinz
,
Cronin, Jacqueline
in
Adenosine Monophosphate - analogs & derivatives
,
Adenosine Monophosphate - pharmacology
,
Alanine - analogs & derivatives
2020
SignificanceMiddle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.
The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
Journal Article
Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters
by
Feldmann, Heinz
,
Rosenke, Rebecca
,
Baseler, Laura
in
Alveolar Epithelial Cells - virology
,
Animals
,
Antigens
2016
Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B).
Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi.
Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.
Journal Article
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1
by
Tamin, Azaibi
,
van Doremalen, Neeltje
,
Gerber, Susan I
in
Aerosols
,
Bayes Theorem
,
Betacoronavirus - pathogenicity
2020
In this research letter, investigators report on the stability of SARS-CoV-2 and SARS-CoV-1 under experimental conditions. The viability of the two viruses was assessed in aerosols and on plastic, stainless steel, copper, and cardboard.
Journal Article
Nipah@20: Lessons Learned from Another Virus with Pandemic Potential
by
Broder, Christopher C.
,
Lee, Benhur
,
Saville, Melanie
in
Animals
,
Betacoronavirus - pathogenicity
,
CEPI
2020
Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential. Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.
Journal Article