Vol. 252 March 15, 2021 COVID-19 Variants and Vaccines

“When an infected cell builds new coronavirus, it occasionally makes small copying errors, called mutations, in the letters of RNA that make up the coronavirus genome.” The coronavirus genome mutations result in changes in the proteins making up its spikes.
– NY Times Feb. 16, 2021, D2, Jonathan Corum and Carl Zimmer

The coronavirus responsible for Covid-19 and the influenza virus causing seasonal flu both mutate into different versions of themselves, but in very different ways. The new COVID-19 viruses are called “variants” while, if you remember, the flu virus annual mutations are called “strains”. The difference between a “variant” and a “strain” is significant.

The flu virus strain that appears annually is basically a whole different virus from the flu virus of the preceding year. Remember the “H”s and “N”s? The swine flu was  H1N2 ( maybe, I forget), Avian flu was H2N2 (maybe) and another was H1N3 (I think). The Hs and Ns referred to different combinations of whole proteins that allowed the flu virus to enter our cells, replicate, and cause flu symptoms. Once any year’s new protein sequence of whole flu virus was identified in the southern hemisphere, where it always first appears, the development of a vaccine to block that particular virus from attacking our cells is launched.

The COVID-19 virus mutations consist of only a few changes in its spike proteins, not the whole virus. It’s the spikes that allow the coronavirus to attach to our cells, replicate itself, and release copies of itself into our blood stream to cause symptoms. All three of our current vaccines are directed at instructing our body to generate antibodies to the spike proteins, so that attachment to our cells does not occur. The changes (mutations) in the spike protein occur only in a few peptides (protein building blocks) in a spike while the rest of the coronavirus remains the same. Hence it is a “variant”, not a new “strain”.

Below is a depiction of one of the now familiar coronavirus spikes consisting of three proteins winding around themselves like a tangled telephone cord. Changes in a small number of peptides in this tangled mass creates several variants of spikes that are better then the original virus in attaching to human cells.
Imagine that just three of the yellow spots in this depiction of the spike proteins were changed to red. That is the magnitude of the change in the spike protein. These spike protein changes, quickly identified by protein scientists, were named for the location in which the mutation first appeared. So, we have a British (or U.K.) variant, a Brazilian variant (actually first identified in several Japanese citizens returning from a trip to Brazil), and a South African variant.

The variant’s scientific names are based on the location of the few peptide changes in one of the three spike proteins:
British variant – three mutations in the B.1.1.7 spike (now detected in 39 states in the U.S.),
South Africa variant – three mutations in the B.1.351 spike (in 20 other countries and 7 states),
Brazil variant- three mutations in the P.1 spike (in 18 countries and 6 states).
Some of the mutations are shared by the variants and some are unique to each one. Other variants, like the New York variant, continue to be detected.

I have listed these seemingly arcane designations because the spike-numbered names are being used by some media rather than the country’s name of first detection, unlike the original COVID virus being xenophobically labeled the “Chinavirus”.  (What a difference is made by a change in administration and a year of public and media learning! )These variant names give us a clue as of to how specific and complicated proteomics (the science of proteins) has become. It also serves as a reminder to us that, as is often the case in science, the “devil is in the details.”

The Moderna and Pfizer vaccines use messenger RNA (mRNA) to inject anti-spike antibody-making genetic instructions into our cells while the Johnson & Johnson vaccine uses a no-symptom-producing cold virus to carry those instructions into our cells. The newer technology mRNA vaccines are fragile and need very cold temperatures to remain stable. The Johnson & Johnson vaccine, using the older technology of a whole-virus carrier, is stable at room temperature for much longer.

Better spike attachment by the virus variants translates into being more contagiousness and spreading faster. Whether the variants will cause more symptoms, greater severity, or the possibility of reinfection is currently unknown. Limited, early studies of the variants suggests that some of the spike mutations MAY make our current vaccines somewhat less effective in enticing antibody responses.  “These new studies have yet to be published in scientific journals. Their authors caution that findings on cells in laboratories do not always translate to the real world.” (Boston Globe March 3, 2021, A9, Cal Zimmer)

We do know that more vaccines are being developed using a number of different technologies. I believe that all of them are directed at spike proteins so that spike mutations will remain a consideration, but maybe not. I just heard of an emerging COVID vaccine that does not need to be injected into your arm; it’s a patch. The story continues.

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