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Member since: Fri Sep 17, 2004, 03:59 PM
Number of posts: 67,637

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The story behind COVID-19 vaccines -by Anthony S. Fauci


Science 09 Apr 2021:
Vol. 372, Issue 6538, pp. 109
DOI: 10.1126/science.abi8397

Amid the staggering amount of suffering and death during this historic pandemic of COVID-19, a remarkable success story stands out. The development of several highly efficacious vaccines against a previously unknown viral pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in less than 1 year from the identification of the virus is unprecedented in the history of vaccinology. A frequently asked question is how such an extraordinary accomplishment could have been realized in such a short time frame, when timelines for other vaccines are measured in years if not decades. In fact, concern about this truncated timeline has contributed in part to the hesitancy in accepting these vaccines. What is not fully appreciated is that the starting point of the timeline for SARS-CoV-2 vaccines was not 10 January 2020, when the Chinese published the genetic sequence of the virus. Rather, it began decades earlier, out of the spotlight.

Two activities predate the successful COVID-19 vaccines: the utilization of highly adaptable vaccine platforms such as RNA (among others) and the adaptation of structural biology tools to design agents (immunogens) that powerfully stimulate the immune system. The RNA approach evolved over several years owing to the ingenuity of individual scientists, including Drew Weissman and Katalin Karikó, and the concentrated efforts of several biotech and pharmaceutical companies.

The discovery of an immunogen adaptable to the multiple platforms (messenger RNA and others) used for COVID-19 vaccines resulted from collaboration across different scientific subspecialities. At the Vaccine Research Center (VRC) of the U.S. National Institute of Allergy and Infectious Diseases, a group led by Peter Kwong had for several years used tools of structure-based vaccine design to determine the optimal structural conformation of a trimeric protein on the surface of the virus (the envelope protein) that allows HIV to bind to cells and ultimately trigger the production of antibodies that neutralize many HIV viral strains. Although this sophisticated approach has not yet led to a successful HIV vaccine, it caught the attention of another VRC investigator, Barney Graham, who was interested in generating a vaccine for respiratory syncytial virus (RSV). Graham joined Jason McLellan (of Kwong's team) to adapt a structure-based approach to an RSV vaccine. They identified the prefusion conformation of the viral spike protein as highly immunogenic and created mutations to stabilize that conformation for successful use as an immunogen. This was a huge step toward the creation of a successful RSV vaccine.

VRC researchers and colleagues then built on the RSV advances. Graham's team, including Kizzmekia Corbett, and collaborators in the laboratories of McLellan and Andrew Ward adopted this approach of mutational stabilization of prefusion proteins in their work on the spike protein of the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). So, when the genetic sequence of the SARS-CoV-2 became available, Graham's team lost no time in joining their long-time collaborators at Moderna to develop an RNA vaccine using a stabilized, prefusion spike protein as the immunogen. Pfizer and BioNTech, where Karikó was working, also used the RNA platform that she and Weissman had perfected and the immunogen designed by Graham to develop an RNA vaccine. Additional companies also used Graham's immunogen in other vaccine platforms that had been evolving for years, to make SARS-CoV-2 vaccines.

SARS-CoV-2 vaccines based on the new immunogen rapidly moved to clinical trials. Several of these vaccines were tested in phase 3 efficacy trials at a time when the level of community spread of SARS-CoV-2 was extremely high, allowing vaccine efficacy endpoints of greater than 90% to be reached in a timely fashion. The speed and efficiency with which these highly efficacious vaccines were developed and their potential for saving millions of lives are due to an extraordinary multidisciplinary effort involving basic, preclinical, and clinical science that had been under way—out of the spotlight—for decades before the unfolding of the COVID-19 pandemic. When the stories and recounting of this pandemic are written, it is important that this history not be forgotten, as we are reminded once again of the societal value of a sustained and robust support of our scientific enterprise.

This is an article distributed under the terms of the Science Journals Default License.

Also This too from NYT:

I admit to not watching the George Floyd trial because I have been too anxious about the verdict

then I saw THIS and it seems to me that justice MUST prevail.

“The toe of his boot is no longer touching the ground, this means that all of his body weight is being directed down at Mr. Floyd’s neck,” testified Dr. Tobin. This visual presented during court says a lot.

Trump-Style Voting



But Dear Mr. Boehner, what is this "Republican sanity" of which you speak? When did it reign?

But Dear Mr. Boehner, what is this “Republican sanity” of which you speak? When did it reign? Not on your watch. You invited in the crazies and gave them a big bear-hug. You validated their fears and conspiracies. You set them on a path that not so surprisingly ended up with a Republican president inciting a Republican crowd to ransack the citadel of American democracy where you once worked. So spare us your righteous indignation. As you stare deeply into that purplish red sea in your glass, attempt to come to terms with the fact that you once had a chance to try to protect your party and country from insanity and extremism. Instead, you said, “Pour me another.”

Way More:

Biden: "Is That Not Infrastructure"?

President Biden: "How many of you know when you send your child to school the fountain they're drinking out of is not fed by lead pipe? How many of you know the school your child is in still has asbestos in the walls? Is that not infrastructure?

Biden argues trains and highways once weren't seen as infrastructure, but the definition has always changed to meet the moment: "The idea of infrastructure has always evolved to meet the aspirations of the American people and their needs. And it is evolving again today."

President Biden on his infrastructure proposal: "We will not be open to doing nothing. Inaction is simply not an option."


Biden to unveil long-awaited executive action on guns

President Joe Biden is expected to unveil a long-awaited package of executive actions to curb gun violence Thursday at the White House, according to four people familiar with the plan.

The announcement comes nearly three months into Biden’s term in office, a delay that had frustrated activists who wanted the president to fulfill a campaign pledge to take action on gun violence on his first day in office. That frustration only grew after a slate of mass shootings in Colorado, Georgia and California.


WaPo's Philip Bump charts-literally-the astonishing collapse of The Former Guy as a media sensation

For about half an hour Tuesday, a former president of the United States appeared on television to offer his unfiltered assessment of the state of American politics, of foreign policy and of the various controversies flitting around the political world. You probably missed it, because it was Donald Trump offering the same pudding of rhetoric we’ve heard so often to an anchor on the far-right network Newsmax. It was to presidential appearances what a pre-dusk set at the Indiana State Fair would be to Kid Rock.

I heard part of Trump’s spiel and thought about highlighting the ways in which his nonsensical claims about the 2020 election being stolen (it wasn’t) have evolved slightly. I’ve written before about how the Republican Party has seized on the idea that changes made to election processes before the contest were unconstitutional, as a way of implying wrongdoing by Democrats without embracing Trump’s obviously untrue claims about fraud. So Trump has seized on those, too, presenting them as another part of his pride-preserving all-you-can-eat buffet of dishonesty.


Then, So Be It.

So true.

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