Theoretical prediction of the effect omicron mutations on monoclonal antibodies by @jbloom_lab
Authors believe that this combination of mutations located on the RBD could potentially reduce the effect of monoclonal antibodies targeting that area of the virus.
This study is based on the apparent individual & additive effect of mutations based on a computer model of the RBD.
They did a computational method called “deep mutational scanning” which is used to study multiple mutations at once.
It is however not a biophysical model.
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Authors conclude
“Sites 484, 446 & 417 are the biggest drivers of this antigenic change, although other mutations also contribute. Mutations at sites 346, 378, 444 & 504 could make it worse”
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While such computational studies are important in adding information, they do not necessarily predict the real biology of:
1) the whole immune process in the human body especially in vaccinated people/prior infection
2) the remote effect of mutations that occur outside RBD
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Authors however find that the Omicron variant’s calculated score is about the same as a polymutant spike (PMS20) that was artificially engineered in a pseudovirus to maximize escape antibodies.
This was previously substantiated through neutralising studies using PMS20 spike.
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At this time we need to understand that regardless of the Greek name, the virus is the same one that started the pandemic in 2019, ~like the same car with a few custom alterations.
As it adapts to its new found human host, let’s wait for peer-reviewed clinical studies.
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🔹Longer 4 month interval between doses generated stronger immune response (mRNA, humoral) than 1 month (16 vs. 4 weeks)
This ~explains the quick waning in nations that used short gap
🔹1 dose might be enough for those who had prior infection (2nd dose did not add much)
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The study strengthens the original concepts that:
1. Single dose might suffice for those with prior infection
2. Vaccination for COVID-19 is basically a 2-step process, with a 3rd encounter not adding anything substantial. (The “booster dose” might have served as 2nd dose)
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In other words, the first 2 doses of mRNA vaccine, taken “too close together” (3-4 weeks), might have been interpreted by the body as a SINGLE dose.
That will explain why the 3rd mRNA dose generated substantial rise in antibody level afterwards, during the booster campaign.
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Unfortunately, superficial reading & blindly following the narrative of published articles leads the reader to arrive at wrong assumptions.
One MUST take the time & look at the data presented, independently, using basic tools. I have added my notes for those interested.
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❗️The hospitalisation trends at any time must be interpreted in the context of the prevailing vaccination rates. I have used vaccination rates at the beginning of each time period.
It is only basic math, and my notes are self explanatory.
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The fact that people are vaccinated will not make much difference when there is a massive viral load in the air as people talk, sing & spend a long time together in a closed space.
(Mucosal immunity doesn’t last long after vaccination)
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Similar story from Germany recently. Dr Christian Drosten retweeted this story.
Just to show that “3G” will not work against the SARS-CoV-2 virus. See thread for details.
The 3rd dose used were AstraZeneca, Pfizer, Moderna, Valneva (French inactivated vaccine), J&J, CureVac (mRNA), NovaVax (subunit, Spike protein).
They measured antibody level & T cell response after this dose, and compared between various combinations. See paper for graphs.
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The first thing we must remember is that antibody level is not an exact correlate of how much protection is achieved.
In other words, if “double” the antibody level is produced by a particular vaccine, it does not mean that symptomatic infection rate will be “cut in half”.
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