Coronavirus - The Mutated Strain

In our third Q&A segment on COVID-19, Cambiar Senior Analyst Charmaine Chan provides insights into the mutated version of the virus and the efficacy of vaccines.

Describe the new mutated strain of COVID that has emerged in the U.K.

This strain B.1.1.7 was first identified in September 2020, but is now dominant in the U.K. causing the most severe lockdowns in the country (e.g. headlines of “Christmas is cancelled”, “40+ countries banning flights from the U.K.”).

Researchers have notedI:

  1. This strain represents a lineage that shows adaptive (vs just random) mutations that could be worrisome,
  2. Protein-protein modeling and animal studies indicate that amongst the 17 unique mutations in this strain, some are likely to increase transmission and infectivity.
  3. The observations that this is ‘more deadly’ and ‘increased ability to infect younger populations’ are preliminary at this point.

Fig 1. B.1.1.7 strain has accumulated more mutations than is expected from the basal rate, suggesting that evolutionary pressures are causing the virus to adapt for fitness/survival. In particular, the N501Y and P681H mutations in the spike protein increases infectivity and virulence of the virusII.

Do vaccines work against these new, adaptively-mutated/truncated strains (e.g. B.1.1.7.)?

Based on our research, we believe they will work with decreasing efficacy until they do not and we need a version 2.0 and so on. This is logical, as both antibodies and T-cells are specific to the sequence/structure of the target (i.e. spike protein). As the virus accumulates mutations, the more likely the structure of the target protein becomes unrecognizable to our immune system. However, as of now, the World Health Organization believes that our newly created vaccines should work well enough vs these new strainsIII.

The hypothetical advantage of mRNA-based vaccines is that as scientists sequence the genomes of these new strains, they can swap out the “cassettes” of the spike proteins (from which our bodies use as instructions to generate antibodies and T-cells against) to reflect these changes for a new version of the vaccine.

However, our ability to thoroughly test the efficacy/safety of subsequent versions of vaccines would be limited. Repeated administration of mRNA-based vaccines might have different risk/reward profiles. While just swapping out the cassettes and making initial new batches might take only 1-2 months, scaling/distribution takes 3 months+, and clinical trials could take 6 months+. In a way, we might always either be:

  1. playing catch-up to emergent strains, or
  2. making predictions on what new strains might emerge next season (e.g. similar to updated flu vaccines every year), making subsequent vaccines potentially less effective.

In our COVID update in June (Coronavirus – What You Need to Know II), we discussed that if COVID was not contained quickly, a certain percentage of the population might always be infected, creating fertile ground for the virus to adapt to evolutionary pressures inside their hosts (e.g. patients infected with COVID for long durations). There is a good chance that COVID will be endemic and we have to acclimate/live with it. An optimist would say this is like the common cold or the flu. The pessimist would say we do not quite know what the evolutionary path of this virus is yet.