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@Monkshood, I had a quick look through my notes and thought this might be useful for others as well:
Size of Affimers and Antibodies
". A large binding surface, obtained through two 9 amino acid loops, enables Affimer proteins to bind with high affinity and exquisite selectivity. At 12-14 kDa, Affimer® molecules are around 10 times smaller than antibodies, giving several performances advantages such as increased packing density on surfaces and greater proximity to sensor surfaces." [Avacta website]
Spike Protein Mutations
"Since the Affimer reagents we use in Avacta’s range of SARS-CoV-2 tests do not bind in the region of the spike protein where the dominant mutations appear, we do not anticipate that the performance of the tests will be affected." [Avacta website]
S protein homology
Although Sars-Cov-1 (responsible for ‘01-‘04 SARS outbreak) is also a coronavirus, the Sars-CoV-2 (covid-19) has some distinguishing features. The Spike (S) protein (RBD region) found on both virus surfaces, has only 66% homology between the two strains. The Nucleocapsid (N) protein is significantly higher at 90%.
GLA
I wouldn't imagine them targeting the spike protein without considering the impact of mutations, it would be a mistake. The S protein RBD homology was known between the two strains (Cov1/Cov2). The size comparison does give an advantage such as higher surface packing density and better proximity.
You are going back to March/April last year when they first produced the Affimers. I am not sure how much was known at that point, there was clearly not enough time to provide information about conserved sites although they may have been able to compare it to Sars Cov. If I recall correctly the main focus at the time was specificity, in that it did not cross react with other coronaviruses.
You can argue either way re comparison to antibodies, a larger binding area may also reduce the impact of a change.
We will have to wait until they tell us something but with the standards becoming available and real samples starting to look obtainable we should know soon.
@Monkshood, some good points there. To add, we can assume that affimers were specifically designed to bind regions where dominant mutations do not occur. Antibodies targeting the same antigen, compared to affimers, will have comparatively poor specificity (larger in size) and as such mutations will have a bigger impact on antibodies. Omicron has mutations on the N and S protein and it is not a straight forward comparison. We also know that Avacta was able to detect the Delta variant (and they provided data). Looks like an interesting period ahead.
GL
This refers to the S protein - not the N protein that the majority of the test are based on. The company have not put out anything about the changes in that yet (although there are less) . Note GSKs sotrovimab looks like it may still work so hopefully if the Affimers bind to the same site then all would be well.
Very interesting Monkshood
If I am reading that right could it mean that some of the lft's may not detect as they will be using the antibody that does not bind?
The data is starting to come thorough on Omicron. It would nice to see Avacta update on the performance of their tests with this variant before the New Year.
From SinoBiological-
After screening a panel of previously established spike antibodies, we identified one (mouse) mAb , clone 40592-MM117, strongly reactive with the Omicron Spike protein. There is another antibody that demonstrates moderate reactivity against the Omicron variant. All other tested clones, including several broad-spectrum ACE2-competing neutralizing antibodies, don’t bind with the mutant at all.
It’s noteworthy that clone 40592-MM117 has non-ACE2 competing neutralizing activity against both the original strain and the Delta variant. Interestingly, the other mAb tested reactive to Omicron also has non-ACE2 binding neutralizing activity against previous strains. Whether the same clones can also neutralize the Omicron variant is currently being tested.
ps - I was not serious about using the whole spike as a vaccine (it may even make you more susceptible!).
If you fancy a technical read about vaccines and the resilience of different treatments (and an interesting approach to vaccines) look up RadVaC - Their press release covers the main points re-Omicron but their white paper is a great source for a deeper understanding of the background biology.
Thanks Monkshood...everything crossed here...
I have been informed that standards of the spike protein produced in HEK293 cells (so glycosylate) for Omicron will be available from the 11 th December. Hopefully Avacta will be purchased some to test their LFT's.
At just £360 for 100ug it will also be just in time for making DIY Omicron vaccines to give your loved ones as Christmas presents.
what difference will it make Tim?
Delta was the big deal when it mutated and AVCT detected it and we still don't have a test in the UK or HUA anywhere in the world.
If not then, why now?
says only variants of concern will be tested and Gamma (brazil) was one
https://www.ecdc.europa.eu/en/covid-19/variants-concern
Timster...'we should get some samples at some point:'...one would hope so but according to the Avacta website they are still awaiting the Brazilian variant...!!!
If there’s no longer any prospect of a U.K. Gov contract, we have nothing to lose from a bit of PR a calling upon the Gov to obtain Omicron samples and distribute then to U.K. diagnostics industry. Why can’t Sir Al directly call upon Javid to supply samples that would allow them to cook up accurate affimers in a matter of weeks?
Govt ignored Mologic until they went public with their frustrations.
we should get some samples at some point:
Avacta® Diagnostics monitors the emergence of new SARS-CoV-2 Variants of Concern (VOC) using the Public Health England (PHE) and World Health Organisation (WHO) lists. A Variant of Concern is one that has been shown to be associated with one or more of the following changes:
Increase in transmissibility or detrimental change in COVID-19 epidemiology
Increase in virulence or change in clinical disease presentation
Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.
When a variant is designated as a VOC, Avacta® obtains the irradiated virus, when it becomes available, and tests it on the AffiDX® SARS-CoV-2 Antigen Lateral Flow Test.
It sure does. In a way that allows us to accurately (100%) detect the delta VOC, whereas the others don’t.
Certainly different. Clearly better.
All of the licensed tests that detect N don’t accurately detect delta. I.e. due to the mutation of the N.
What are you implying Ndn?
There are also mutations in the N-protein, albeit not as many as in the spike so all antigen tests will need checked.
https://www.bbc.co.uk/news/health-59460252
Rapid or lateral flow tests, which can be used at home, can't tell you which variant you're infected with - but they are still thought to be able to tell you if you're negative or positive, even with Omicron.
just need the gov to provide some samples so we can definitively state that Affidx detects it!