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SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape
nature.com ^ | July 14,2021 | Tyler N. Starr, Nadine Czudnochowski, […]Gyorgy Snell

Posted on 09/06/2021 10:35:00 PM PDT by NoLibZone

ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1,2,3, have activity against diverse sarbecoviruses4,5,6,7, and be highly protective through viral neutralization8,9,10,11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics. Main

The most potently neutralizing antibodies to SARS-CoV-2—including those in clinical use14 and dominant in polyclonal sera15,16—target the spike RBD. Mutations in the RBD that reduce binding by antibodies have emerged among SARS-CoV-2 variants17,18,19,20,21, highlighting the need for antibodies and vaccines that are robust to viral escape. We have previously described S3094, an antibody that exhibits potent effector functions and neutralizes all current SARS-CoV-2 variants22,23 and the divergent sarbecovirus SARS-CoV-1. S309 forms the basis for an antibody therapy (VIR-7831, recently renamed sotrovimab) that has received emergency use authorization from the US Food and Drug Administration for treatment of COVID.

Study:

https://www.nature.com/articles/s41586-021-03807-6.pdf

(Excerpt) Read more at nature.com ...


TOPICS: News/Current Events
KEYWORDS: covid19; covidantibody; nlz; s2h97; s309; sotrovimab

1 posted on 09/06/2021 10:35:00 PM PDT by NoLibZone
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To: NoLibZone

Antibody treatments - bump for later....


2 posted on 09/06/2021 10:37:32 PM PDT by indthkr
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To: NoLibZone; All
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3 posted on 09/06/2021 10:42:11 PM PDT by musicman (The future is just a collection of successive nows.)
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To: indthkr

Just take ivermectin with zinc, vit D, Vit C, quercetin.

Even the “horse paste” 1.87% works. I used it when sick as have others I know. No problems at all with it.


4 posted on 09/07/2021 3:18:16 AM PDT by Captain7seas
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To: musicman

Reportedly monoclonal antibodies are effective against COVID-19. The thing which stands in their way is administering them with blood infusion. Blood infusion takes up hospital resources which are needed for treating sick people in the middle of a pandemic. Add to that, blood infusion requires pumping a patient’s blood out, mixing it with the drug, and pumping the blood back into the patient. I can’t be alone in reserving a procedure like blood infusion for something which threatens my life, and not for a protecting me against serious illness which probably won’t affect me anyway.


5 posted on 09/07/2021 6:24:39 AM PDT by nagant
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To: Captain7seas

“Next, we determined the prophylactic efficacy of S2H97 in vivo using a Syrian hamster model of infection. We administered hamsters with 25 mg kg−1 S2H97 2 days before intranasal challenge with SARS-CoV-2 and assessed viral RNA load and infectious viral titres in the lungs 4 days after infection. S2H97 prophylaxis reduced the number of RNA copies by more than 10,000-fold relative to control in the four hamsters that had detectable circulating antibody levels at the time of challenge, and reduced infectious viral titres to the lower detection limit in these hamsters (Fig. 2f). The two hamsters not exhibiting a reduction in viral load had circulating S2H97 levels below the limit of quantification (50 ng ml−1) at the time of viral challenge (Extended Data Fig. 6h), which may reflect a failure in the intraperitoneal administration procedure. Therefore, S2H97 demonstrates that antibodies to the newly identified antigenic site V can be protective in vivo.”

This is what to zone in on. They found an antibody to a cryptic site that prevented entry at the ACE entry site. Using this strip of peptide that binds to S2H97 (site V) could be powerful in vaccination....


6 posted on 09/07/2021 6:36:31 AM PDT by Frank Sheed (The injustice of trendiness is nearly dualistic in its isomorphism.)
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To: nagant

The FDA not long ago authorized administration of the Regeneron monoclonal antibodies via injection (in certain circumstances).


7 posted on 09/08/2021 4:25:04 AM PDT by ProtectOurFreedom (“Criminal democrats kill babies. Do you think anything else is a problem for them?”)
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