Differential Modification of Development of Preneoplastic Lesions in the Syrian Golden Hamster Initiated With a Single Dose of 2,2′-Dioxo-N-nitrosodipropylamine: Influence of Subsequent Butylated Hydroxyanisole, α-Tocopherol, or Carbazole23

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S390-S390
Author(s):  
Anna Kushnir ◽  
Steffen Mueller ◽  
Sybil Tasker ◽  
J Robert Coleman

Abstract Background Although multiple COVID-19 vaccines are currently in use, emergence of novel SARS-CoV-2 variants with reduced neutralization raises concern of future vaccine escape. COVI-VAC™ is a live attenuated SARS-CoV-2 strain based on WA/1 being developed as an intranasal COVID-19 vaccine. COVI-VAC is attenuated through removal of the furin cleavage site and introduction of 283 silent, deoptimizing mutations that maintain viral amino acid sequence but slow viral replication in vivo by up to 5 logs. Notably, COVI-VAC presents all viral antigens in their native conformation and is not limited to spike. COVI-VAC demonstrated attenuation, immunogenicity and single dose protection in both the Syrian golden hamster and non-human primate models and currently in Phase 1 clinical trials. In this study, we evaluated efficacy of COVI-VAC against challenge with the Beta/B.1.351 variant in Syrian golden hamsters. Methods Syrian golden hamsters, 7-10 weeks of age were, vaccinated intranasally with 8.25x104 PFU COVI-VAC (n=28) or vehicle control (n=16). Twenty seven days post-vaccination, animals were challenged intranasally with 3x104 PFU of wildtype (WT) SARS-CoV-2 Beta. Animals were weighed daily. Further analysis is being conducted with serum and key tissues from pre and post challenge timepoints to include neutralizing antibody, biodistribution (subgenomic qPCR) and histopathology. Results COVI-VAC prevented weight loss following challenge with the heterologous variant of SARS-CoV-2, B.1.351/Beta (Figure). Results of additional analyses will be available before the IDWeek meeting. Change in Weight following SARS-CoV-2 Beta Challenge Conclusion COVI-VAC is protective against heterologous challenge with SARS-CoV-2 Beta. By presenting all viral antigens, COVI-VAC may be less affected by viral evolution than spike-based vaccines. Disclosures Anna Kushnir, PHD, Codagenix Inc (Employee) Steffen Mueller, PhD, Codagenix Inc (Board Member, Employee, Shareholder) Sybil Tasker, MD, MPH, FIDSA, Codagenix Inc (Employee, Shareholder) J. Robert Coleman, PhD, Codagenix Inc. (Board Member, Employee, Shareholder)


1992 ◽  
Vol 166 (3) ◽  
pp. 309-319 ◽  
Author(s):  
SHUKO TAKAGI ◽  
HIROSHI MANO ◽  
MASASHI TSUNODA ◽  
HIROTO NAKADAIRA ◽  
KAZUO ENDOH ◽  
...  

Pancreas ◽  
2004 ◽  
Vol 29 (4) ◽  
pp. 320-323 ◽  
Author(s):  
Ajit T. Abraham ◽  
Sudeep R. Shah ◽  
Brian R. Davidson

The Hamster ◽  
1985 ◽  
pp. 289-321 ◽  
Author(s):  
Thomas A. Schoenfeld ◽  
Christiana M. Leonard

Chemosphere ◽  
1986 ◽  
Vol 15 (4) ◽  
pp. 519-533 ◽  
Author(s):  
Martin van den Berg ◽  
Erik de Vroom ◽  
Kees Olie ◽  
O. Hutzinger

2021 ◽  
Vol 11 ◽  
Author(s):  
Voddu Suresh ◽  
Deepti Parida ◽  
Aliva P. Minz ◽  
Manisha Sethi ◽  
Bhabani S. Sahoo ◽  
...  

The Syrian golden hamster (Mesocricetus auratus) has recently been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers these models’ optimal use. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin-converting enzyme 2, a proven functional receptor for SARS-CoV-2 in different organs of the hamster. Using two different antibodies (MA5-32307 and AF933), we have conducted immunoblotting, immunohistochemistry, and immunofluorescence analysis to evaluate the ACE2 expression in different tissues of the hamster. Further, at the mRNA level, the expression of Ace2 in tissues was evaluated through RT-qPCR analysis. Both the antibodies detected expression of ACE2 in kidney, small intestine, tongue, and liver. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine were negative for ACE2 expression. Analysis of tissues from different age groups and sex didn’t show any obvious difference in ACE2 expression pattern or level. Together, our findings corroborate some of the earlier reports related to ACE2 expression patterns in human tissues and contradict others. We believe that this study’s findings have provided evidence that demands further investigation to understand the predominant respiratory pathology of SARS-CoV-2 infection and disease.


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