I am curious how our scientists and governments can best respond to this news
What would make the new strain more virulent, more contagious? Any idea? Could it aerosolize more easily or what, I wonder.
I found this summary in Up to Date:
● VUI-202012/01 – A variant under investigation (VUI), 202012/01, which is also referred to as lineage B.1.1.7, was first identified in the United Kingdom in late 2020 and was temporally associated with an increase in regional infections . It has subsequently been identified in other countries, including the United States. This variant contains more than a dozen mutations compared with reference genomes, with several within the spike protein. One of these polymorphisms, N501Y, is located in the receptor-binding domain and has been demonstrated to increase SARS-CoV-2 infectivity in a mouse model . Reports of preliminary epidemiologic and virologic analyses of this variant suggest that it is associated with a higher respiratory tract viral load and increased transmissibility in humans compared with other variants [13,15]. However, data are limited, and the possibility that the increased spread of this variant in the United Kingdom reflects other factors has not been excluded. Data are also too limited to indicate whether this variant could negatively impact disease severity or vaccine response, but there has been no evidence of this thus far.
McIntosh, Kenneth; Martin Hirsch and Alison Bloom: Coronavirus disease 2019 (COVID-19): Epidemiology, virology, and prevention
It sounds like so far, there is no evidence the vaccine will be any less effective against this variant (it is early times, though)
Yes, thanks. It occurred to me that it might have something to do with the spike protein making it infect cells more easily, but I kind of discounted that intuitively (but incorrectly) because the mRNA vaccines lead to duplicating a part of the spike, if I understand correctly. But the spike is a pretty complex little bundle. Pessimistically, it seems (again, intuitively) that it wouldn’t necessarily take a lot to mutate it so that the vaccines are ineffective against it. Of course, I know zip about the molecular biophysics and biochemistry.
A good thing – again, if i understand correctly – is that the mRNA vaccines are relatively easy to modify. There still would be the extensive trials required, though.
the mutation in the RBD (receptor bindingdomaine) region of the spike protein might increase the binding affinity against the ace2. The virus is promiscuous in that region which is what allowed it to jump the species. An increase in binding affinity will lead to a higher infection success.
COG-UK update on SARS-CoV-2 Spike mutations of special interest
Prepared by COG-UK, 20 t h December 2020
“Potential biological significance of mutations B.1.1.7 lineage. This variant has 23 mutations with 14 amino acid replacements and 3 in-frame deletions which are listed in Table 1b. Two of these mutations have already been described to alter SARS-CoV-2 biology: N501Y sits in the receptor binding motif (RBM) of the Spike protein, and has been described to increase binding affinity to the human ACE-2 receptor; 69-70del has been identified in variants associated with immune escape in immunocompromised patients and is responsible for a “dropout” in the S gene PCR target in certain diagnostic tests (e.g. Thermo Fisher TaqPath). These tests target multiple regions of the virus genome, so the test itself is not compromised. Reported cases and phylogenetic analyses have indicated an exceptional rate of introduction of mutations into this lineage. It has been hypothesised that this lineage may have resulted from the transmission of the virus from a chronically infected individual. This is based on observations that a high rate of mutations may accumulate in immunocompromised patients with chronic infections of SARS-COV-2.”
An increase in binding affinity means higher probablity of the virus to find it’s target before being washed away into your stomach by the mucous clearing system.
What region(s) of the spike protein are targeted via mRNA vaccines relative to the “receptor binding motif”? As I was wondering out loud above, how likely would you think successive mutations might be in diminishing or disabling immune response to a vaccine?
unfortunately I do not know the sequence of the vaccine but when we evaluated early cases using arrays with short peptide sequences it became clear that antisera from before Nov 2019 only flagged a small number of sequences due to crossreactivity whilst those who were infected had antibodies to many more fragments of the proteins.
https://www.medrxiv.org/content/10.1101/2020.11.23.20235002v1.full is a paper from serimmune on this subject demonstrating the breadth of the immune response and how the virus mutates to evade the immune response. After all, that is why we have to revaccinate against the new flu strains.
The Pfizer vaccine uses the whole spike protein.
This topic was automatically closed 6 days after the last reply. New replies are no longer allowed.