Passive transfer of poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose glucan protection against lethal infection in an animal model of intra-abdominal sepsis.

1996 ◽  
Vol 64 (6) ◽  
pp. 2201-2205 ◽  
Author(s):  
R L Cisneros ◽  
F C Gibson ◽  
A O Tzianabos
2018 ◽  
Vol 4 (3) ◽  
pp. 438-446 ◽  
Author(s):  
Su-Jin Park ◽  
Young-Il Kim ◽  
Angela Park ◽  
Hyeok-Il Kwon ◽  
Eun-Ha Kim ◽  
...  

Science ◽  
2020 ◽  
Vol 369 (6506) ◽  
pp. 956-963 ◽  
Author(s):  
Thomas F. Rogers ◽  
Fangzhu Zhao ◽  
Deli Huang ◽  
Nathan Beutler ◽  
Alison Burns ◽  
...  

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.


2012 ◽  
Vol 93 (6) ◽  
pp. 1288-1293 ◽  
Author(s):  
Xiao-Ping Chen ◽  
Mei-Li Cong ◽  
Ming-Hui Li ◽  
Yan-Jun Kang ◽  
Yan-Meng Feng ◽  
...  

A novel tick-borne bunyavirus (Huaiyangshan virus, HYSV), which causes haemorrhagic fever-like disease, has recently been reported in China. So far no animal experiments have been performed to study its pathogenesis. Towards developing an animal model for HYSV fever, newborn and adult mice and rats and golden hamsters were inoculated intracerebrally or intraperitoneally with HYSV. Newborn rats and newborn mice, especially Kunming (KM) mice, appeared highly susceptible. Remarkably, the KM mice that died of the HYSV infection developed large necrotic areas in the liver, while no obvious pathological changes were observed within the other organs. PCR and immunohistochemical analyses of the post-mortem material detected both HYSV antigen and RNA in almost all organs, indicating a systemic infection. Our data demonstrate that HYSV can cause a lethal infection of both newborn mice and newborn rats with apparent pathological damage of the liver. This animal model may help to understand the pathogenesis of the HYSV infection in humans.


Author(s):  
Thomas F. Rogers ◽  
Fangzhu Zhao ◽  
Deli Huang ◽  
Nathan Beutler ◽  
Alison Burns ◽  
...  

ABSTRACTThe development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.


2021 ◽  
Vol 6 (1) ◽  
pp. e000636
Author(s):  
Rachel L O'Connell ◽  
Glenn K Wakam ◽  
Ali Siddiqui ◽  
Aaron M Williams ◽  
Nathan Graham ◽  
...  

BackgroundTrauma and sepsis are individually two of the leading causes of death worldwide. When combined, the mortality is greater than 50%. Thus, it is imperative to have a reproducible and reliable animal model to study the effects of polytrauma and sepsis and test novel treatment options. Porcine models are more translatable to humans than rodent models due to the similarities in anatomy and physiological response. We embarked on a study to develop a reproducible model of lethal polytrauma and intra-abdominal sepsis, which was lethal, though potentially salvageable with treatment.MethodsOur laboratory has a well-established porcine model that was used as the foundation. Animals were subjected to a rectus crush injury, long bone fracture, liver and spleen laceration, traumatic brain injury and hemorrhage that was used as a foundation. We tested various colon injuries to create intra-abdominal sepsis. All animals underwent injuries followed by a period of shock, then subsequent resuscitation.ResultsAll animals had blood culture-proven sepsis. Attempts at long-term survival of animals after injury were ceased because of poor appetite and energy. We shifted to an 8-hour endpoint. The polytrauma injury pattern remained constant and the colon injury pattern changed with the intention of creating a model that was ultimately lethal but potentially salvageable with a therapeutic drug. An uncontrolled cecal injury (n=4) group resulted in very early deaths. A controlled cecal injury (CCI; n=4) group had prolonged time prior to mortality with one surviving to the endpoint. The sigmoid injury (n=5) produced a similar survival curve to CCI but no animals surviving to the endpoint.ConclusionWe have described a porcine model of polytrauma and sepsis that is reproducible and may be used to investigate novel treatments for trauma and sepsis.Level of evidenceNot applicable. Animal study.


1999 ◽  
Vol 43 (2) ◽  
pp. 413-414 ◽  
Author(s):  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
John R. Graybill

ABSTRACT Weanling outbred rats were infected with Cryptococcus neoformans by direct percranial puncture and inoculation into the cranium. A lethal infection ensued. Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue. Weanling rats are an acceptable model for the study of central nervous system infection with C. neoformans.


1999 ◽  
Vol 67 (11) ◽  
pp. 6168-6172 ◽  
Author(s):  
Thomas C. Zahrt ◽  
Nancy Buchmeier ◽  
Stanley Maloy

ABSTRACT Hybrid derivatives of closely related bacteria may be used to dissect strain-specific functions that contribute to virulence within a host. However, mismatches between DNA sequences are a potent barrier to recombination. Recipients with mutS and recDmutations overcome this barrier, allowing construction of genetic hybrids. To determine whether Salmonella hybrids constructed in a mutS recD host can be used to study virulence, we assayed the effect of mutS andrecD mutations on the virulence of Salmonella typhimurium 14028s in mice. Mutants defective in eithermutS or recD do not affect the time course or the 50% lethal dose (LD50) of the infection. In contrast, the inactivation of both mutS and recD results in a synthetic phenotype which substantially increases the time required to cause a lethal infection without changing the LD50. This phenotype results from an inability ofmutS recD double mutants to rapidly adapt to purine-limiting conditions present within macrophages. Although the disease progression is slower, S. typhimurium mutS recDmutants retain the ability to cause lethal infections, and, thus, hybrids constructed in mutS recD hosts may permit the analysis of virulence factors in a surrogate animal model.


1999 ◽  
Vol 73 (1) ◽  
pp. 783-786 ◽  
Author(s):  
Alison J. Johnson ◽  
John T. Roehrig

ABSTRACT Several dengue (DEN) virus vaccines are in development; however, the lack of a reliable small animal model in which to test them is a major obstacle. Because evidence suggests that interferon (IFN) is involved in the human anti-DEN virus response, we tested mice deficient in their IFN functions as potential models. Intraperitoneally administered mouse-adapted DEN 2 virus was uniformly lethal in AG129 mice (which lack alpha/beta IFN and gamma IFN receptor genes), regardless of age. Immunized mice were protected from virus challenge, and survival times increased following passive transfer of anti-DEN polyclonal antibody. These results demonstrate that AG129 mice are a promising small animal model for DEN virus vaccine trials.


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