Pre-clinical Evaluation of Hemoglobin Based Oxygen Carriers: Animal Models and Biomarkers

Author(s):  
Paul W. Buehler ◽  
Felice D’Agnillo
Author(s):  
Marina Liu ◽  
Xiongbiao Chen

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of July 31, 2020, there are at least 139 vaccine candidates from around the globe are in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada.


2021 ◽  
Author(s):  
Teresa Lambe ◽  
Alexandra Spencer ◽  
Kelly Thomas ◽  
Stephen Thomas ◽  
Andrew White ◽  
...  

Abstract Vaccines against SARS-CoV-2 are urgently required. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titers were boosted by a second dose. Data from these challenge models and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.


2019 ◽  
Vol 42 ◽  
Author(s):  
Nicole M. Baran

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.


Author(s):  
O. H. Kapp ◽  
M. Ohtsuki ◽  
N. Robin ◽  
S. N. Vinogradov ◽  
A. V. Crewe

Annelid extracellular hemoglobins are among the largest known proteins (M.W = 3.9 x 106), and together with the hemocyanins are the largest known oxygen carriers. They display oxygen affinities generally higher than those o vertebrate hemoglobins with Hill coefficients ranging from slightly higher than unity to values as high as 5-6. These complex molecules are composed of multiple copies of as many as six different polypeptides and posse: approximately 150 hemes per molecule.The samples were diluted to 100-200 μg/ml with distilled water just before application to a thin carbon film (∽15 Å thick). One percent (w/v) uranyl acetate solution was used for negative staining for 2 minutes and dried in air. The specimens were examined with the high resolution STEM. Their general appearance is that of a hexagonal bilayer (Fig. 1), each layer consisting of six spheroidal subunits. The corner to corner hexagonal dimensic is approximately 300 Å and the bilayer thickness approximately 200 Å.


2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.


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