Tuesday, January 26, 2021

Dr. Baric, 2005: humanized mice develop coronavirus respiratory disease

Ralph S. Baric and Amy C. Sims

PNAS June 7, 2005

  For the group 1 coronaviruses, early attempts at developing transgenic mice expressing the hAPN receptor failed to produce a susceptible model, suggesting that other cofactors might be essential for in vivo replication (14).  This outcome is not unique to HCoV-229E  https://www.pnas.org/content/102/23/8073

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  Regeneron said Tuesday that its monoclonal antibody cocktail prevented Covid-19 in a clinical trial.  The news, issued via a press release, mirrored similar news from Eli Lilly last week that its monoclonal antibody prevented symptomatic Covid-19 infections in nursing homes.

  The results represent the first 400 volunteers from the study, which is being run by the National Institute of Allergy and Infectious Diseases (NIAID), and is continuing to enroll patients. The volunteers were at high risk of infection because they lived in the same household as a Covid-19 patient.  Half the patients received a placebo, and the other half received 1.2 grams of casirivimab and imdevimab, Regeneron’s antibodies.  While eight of the 223 patients in the placebo group developed Covid symptoms and tested positive for the virus, none of the 186 patients who received the antibody did.  Volunteers who received the antibody were also less likely to be asymptomatic carriers of the SARS-CoV-2 virus, which causes Covid-19.  Twenty-three volunteers in the placebo group tested positive for the virus, compared to 10 in the antibody group, a 50% reduction….The volunteers were at high risk of infection because they lived in the same household as a Covid-19 patient. https://www.statnews.com/2021/01/26/regeneron-says-monoclonal-antibodies-prevent-covid-19-in-study/

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9-29-20    After months of incredibly hard work by our talented team, we are extremely gratified to see that Regeneron's antibody cocktail REGN-COV2 rapidly reduced viral load and associated symptoms in infected COVID-19 patients," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron…

  To develop REGN-COV2, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. The two potent, virus-neutralizing antibodies that form REGN-COV2 bind non-competitively to the critical receptor binding domain of the virus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science.  https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and

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  Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.

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  humanizing these host strains via surgical implantation of human thymus tissue is required for creation of de novo T cells that can recognize a full complement of human MHC molecules presenting antigens in vivo (Shultz et al., 2012Theocharides et al., 2016Zhao et al., 2015).  Humanized mice such as the bone marrow, liver, thymus (BLT) mouse, generated by co-transplantation of hematopoietic stem cells (HSCs) along with human fetal thymus tissue, offer a powerful translational system to study human immune responses (Hu and Yang, 2012Kalscheuer et al., 2012Lan et al., 2006).  They are particularly useful for virology research, induced pluripotent stem cell (iPSC) immunogenicity studies, and other research requiring functional T cells selected on human self-antigen complexes (Lavender et al., 2013Rong et al., 2014Yu et al., 2007Zhao et al., 2015).  https://www.sciencedirect.com/science/article/pii/S2213671118301024

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8-7-2013   ”When Regeneron's VelocImmune mice were developed, they represented the largest scale precision genetic engineering feat achieved to date," said Andrew Murphy, Ph.D., Senior Vice President Research, Regeneron Laboratories, and a co-inventor of these technologies.  "The scope of the issued claims in these two patents reflects the breadth of Regeneron's contribution to human antibody therapeutics and mouse engineering, and provides Regeneron with important proprietary technology advantages”  https://newsroom.regeneron.com/news-releases/news-release-details/regeneron-granted-fundamental-patents-covering-mouse-antibody

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The humanized "BLT" mouse is created by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own.  The BLT mouse has a fully functioning human immune system.  CREDIT  University of North Carolina School of Medicine   https://www.eurekalert.org/multimedia/pub/44475.php

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https://www.statnews.com/2020/03/05/coronavirus-labs-scramble-to-find-right-animals-for-covid-19-studies/comment-page-1/    maybe focus on health instead of sickness??

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