SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern | Hacker News Reader

SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern

science.sciencemag.org

27 pointsguybedo13 comments

This variant (better known as the epsilon variant) is no longer even classifed as a variant of concern by the WHO [1]. It seems that was likely because it is being dominated by the delta variant.

[1] https://www.who.int/en/activities/tracking-SARS-CoV-2-varian...

+1 Indeed, accounted for back mid June 2021: delta > epsilon (west coast variant): https://youtu.be/xR-LbraMlgs?t=706

Quick -- someone with epidemiology/virology experience -- can we get a summarization for the layman? How concerning is the concern noted in the title?

"Variant of concern" is just a CDC classification which applies to all variants which are interesting enough to require close monitoring, for whatever reason. It is below "variant of high consequence" in the ladder of how worried you should be.

https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-i...

Even Delta is not a "variant of high consequence". There will be extreme reluctance to make that declaration because it would signal that lockdowns and other non-pharmaceutical interventions will be needed for a much longer period than we previously thought.

The WHO is way too political. They could have stopped it right at the start by (advising to) quarantining China from the rest of the world but they decided to play along with China that played down the seriousness (remember that doctor that was being punished by China for revealing the truth). We're still cleaning up their mess. Then with India and the Delta variant the same things happened.

https://www.cp24.com/mobile/world/india-was-warned-of-delta-...

The WHO should be about science not politics. If it's that dangerous they should declare it as such so appropriate measures can be taken. All these things were known in advance but measures not taken because of political or economic concerns.

> They could have stopped it right at the start by quarantining China from the rest of the world

No, they couldn't.

For one thing, WHO doesn't regulate international travel and couldn't quarantine anyone if they wanted to.

(Now, various governments—including the US government which had intelligence on it before China announced anything publicly—could have stopped travel from China, but that's...not the WHO.)

No they don't regulate international travel but they could have publicly come out and said this would have been necessary. Any government sidestepping them would have taken a huge political risk if they had been wrong (and they would have been!). It's a big thing for a government to overrule the WHO.

I'm sure that they would have done it if they had been about science and not about politics. All the knowledge of how serious this was, was there at the start.

I think the discussion of how it came to spread worldwide is even more important than how it emerged in the first place. In particular because we keep making the same mistakes with these variants. The failure to contain the British (Alpha) variant should have been enough warning to up that game. If Delta hadn't spread to Europe and US we would have been in a great situation with current vaccination levels because Alpha was not that dangerous after all.

I'm just worried we will make the wrong choices again for the next one which may be even more destructive. For Delta we're too late. For whatever is next we may not be.

I think you overestimate how well the WHO is run. It has to be political because it is a multinational political entity whether they call themselves that or not.

They don't have willy nilly use of their funding either, and they sometimes have to deal with very difficult heads of state. It's to be expected for an organisation that big, with that size scope to be in a state of semi-chaos no different than a huge multinational.

I totally understand the way they are and how they have become like this. The current political stance has been perfect for the challenges the WHO has dealt with during its lifetime until now. Promoting research, finding funding for affordable medication programs in the third world, things like the COVAX programme that they are promoting now. Some small outbreaks that needed some international coordination and funding. These are the things they used to do and their organisation is perfect for. Until COVID I'm sure not many people had ever even heard of it and that was fine for the work they did which was mostly behind the scenes.

However this crisis requires a different leadership, much more outspoken, more authoritative and quick acting. They could have stepped up to the task but they didn't. The WHO that we have had until now (and has done a great job at what they did) is not the WHO we need now to deal with this massive crisis that is spanning the globe. Just like with climate change this is not something you can leave to individual governments if you are to solve it, because they will only serve their own interests in the end.

I'm sure they will evolve over time. But stronger leadership would have recognised the threat, taken some risk and evolved already. Probably appointed a very visible crisis manager (e.g. an ex-president or other very high-profile executive), and set up a task force with high visibility, strong media communication etc. It would be much harder for governments to ignore and as such much more effective.

I wish they were only as political as a multinational because those do react to threats much better than a truly political organisation does. I'm not saying they're bad at what they do. I'm just saying the WHO we have now is not what we need.

If you use the High consequence classification for delta, what do you use when we're truly fucked?

Delta isn't vaccine resistant and isn't significantly more deadly. Sure it spreads a lot more but most countries are dealing with it just fine.

There probably needs to be a fourth classification between HOC and HOIC but whatever, it doesn't really matter.

Antibodies generated as a response to vaccination that target the SARS-CoV2 binding domain, which is what makes the initial bond with an ACE2 receptor to enter a cell and begin infection, are less effective against some variants that have a modified binding domain. Rather than addressing relative risks, this paper is more about understanding the mechanisms involved which appear to be a combination of modifications to the structure of the binding domain and rearrangement of its disulfide bonds.

From the article: "The acquisition of the L452R substitution by multiple lineages across multiple continents, including the B.1.617.1 and B.1.617.2 lineages emerging in India, is suggestive of positive selection, which might result from the selective pressure of RBD-specific neutralizing Abs"

This is another incremental yet damning piece of evidence suggesting that vaccine induced selective pressure is enhancing the fitness of these variants of concern.

There is growing evidence throughout the peer-reviewed literature suggesting that immune escape is a valid concern [1][2][3][4].

Excerpts from [1]:

- "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control."

- "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?"

- "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection."

- "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape"

- "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"

[1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein (April 2021) https://pubmed.ncbi.nlm.nih.gov/33909660/

[2] Why does drug resistance readily evolve but vaccine resistance does not? (2017) https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...

[3] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens (2015) https://journals.plos.org/plosbiology/article?id=10.1371%2Fj...

[4] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests (2015) https://www.cambridge.org/core/services/aop-cambridge-core/c...

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