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As a mother-to-be, or a father-to-be, you may find yourself particularly concerned about the variants of the ancestral SARS-CoV2 virus —the version of the pandemic virus that has caused most of the cases of COVID-19 over the past year— that have been in the news. You may be following discussions in the news about Pfizer-BioNTech and Moderna mRNA vaccines being fully effective against an increasingly common SARS-CoV2 variant called B.1.1.7 (“UK variant”, which is spreading quickly across the United States) and partly effective against the B.1.351 variant (aka 20H/501Y.V2, “South African”) and partly effective against P.1 (“Brazilian”). If you are really following the story closely, you may know that various other variants of concern are popping up with official number designations as well as nicknames for the geographical locations where they are identified, but you also may have heard that Moderna announced that it has developed and is testing a version of its mRNA vaccine that has been tweaked to create better immunity against the B.1.351 variant, which has appeared in many locations outside of South Africa, including in the United States. The thing tweaked is the sequence of the mRNA, the business end of the vaccine, which, if proved effective in testing, could be used in a booster vaccine, or together with first version of the vaccine to create what’s called a bivalent vaccine. Such a bivalent vaccine could replace the original and also could be used as a booster.
Other tweaked vaccines from other companies are also in the works, but, in the meantime, it’s important to keep in mind that the already-approved vaccines of both Moderna and Pfizer-BioNTech are still the most effective protection against the pandemic. The situation is similar for the Johnson and Johnson vaccine that is on deck for getting emergency use authorization at the time that I am writing this in late February. There are two reasons for this. First, the SARS-CoV2 viruses most likely to infect you in North America are the ancestral ones and increasingly the B.1.1.7, the latter being more contagious and possibly more deadly, but countered as well by the approved vaccines as the ancestral virus. Second, even against the B.1.351 and P.1 variants, the approved vaccines provide some protection, protection that can make the difference between developing a severe, potentially fatal case versus a more mild case —a situation very analogous to what happens frequently with seasonal flu vaccines. We must keep perspective. The 95 percent effectiveness of the Pfizer/BioNTech and Moderna vaccines against the development of COVID-19 after exposure to the ancestral SARS-CoV2 is unusually high for any vaccine. Consequently, we are conditioned to think that some lower percentage of effectiveness of these vaccines against a new variant represents some kind of failure, what it does not. To understand how there can be a sliding scale for vaccine effectiveness with respect to the different variants of SARS-CoV2, let’s delve again into the beautiful world of biology, this time focusing on what it is on the virus, and in the vaccine, that causes an immune response.
Since fetal life, your immune system has developed and learned to ignore cells and molecules that are “self”, meaning part of the body. This is in contrast to an entity that is foreign to the body. In immunology, a foreign entity that can provoke an immune response is called an antigen and very typically antigens are proteins, or proteins that are attached to some other kind of molecule. But —this is an extremely important concept— a given antigen does not provoke a particular immune response, but rather numerous immune responses, each to particular regions of the antigen, known as epitopes. Looking at the spike protein, for instance, the protein that sticks out like spikes from the shell of SARS-CoV2, causing disease and also teaching the immune system to recognize the virus, there are numerous epitopes scattered about this protein. When you are exposed to the virus —or when you are injected with the vaccine, containing mRNA with instructions for your cells to make spike protein and display it on the cell surface so the immune system can start its target practice— it’s not just one target that the immune cells see. Rather, each epitope is a different target. Exposure to such an antigen with its many epitopes generates what’s called a polyclonal immune response. It’s a response that creates a spectrum of different antibody producing cells, called plasma cells (a type of B lymphocyte that is specialized to make antibodies against a specific thing) and different kinds of memory T lymphocytes.
First exposure to an antigen with its various epitopes primes the immune system and the response to all of these epitopes is boosted by the next exposure. Now, the epitopes on a protein antigen exist because of the 3-dimensional structure of the protein, which results, in turn, from the sequence of amino acids that function as building blocks for the protein. Change the identity of a particular amino acid at a particular location in the protein sequence and you may or may not change the shape of an epitope, depending on the location of that changed amino acid in the chain that comprises the protein. Some amino acid spots are more critical than others for doing certain things, such as attaching the spike protein to the ACE-2 receptor on the host’s body cells, or for contributing to an epitope that helps cause an immune response. Not all amino acids in the protein are part of epitopes, but all amino acids are the result of the genetic sequence that encodes the construction of the protein. If the strip of RNA encoding the protein is changed, then one or more amino acids may or may not change. Each change in the RNA strip is called a mutation. This can be the substitution of one letter in the genetic alphabet with a different letter. It also can be the deletion of a letter, or the insertion of an extra letter, although such deletions/insertions are likely to be lethal to the virus, so normally we are talking about substitutions. Occasionally, a mutation, or a set of mutations, will give the virus some advantage that allows it to spread more, in which case such natural selection will favor such mutations and they will become more common. When enough mutations build up so that a version of SARS-CoV2 branches off from its ancestor in the sense that it has new properties, researchers call that new version a variant. That’s what the B.1.1.7, the B .1.351, and the other numbers are; they are variants, versions of the virus that have evolved because various mutations within them have given them an advantage that makes that reproduce more.
In these variants of interests, scientists have found amino acids in particular positions in the spike protein, such as positions 485 and 501, are what have changed most as a result of mutations. Amino acids in such positions are involved in the attachment of the viral spike protein to the ACE-2 receptor, which makes sense, because that’s how the virus gets into cells where it can replicate to make a whole bunch of baby viruses. But while such an evolutionary process has changed some of the epitopes of the spike protein, it has not —so far— changed all of them. Consequently, the already approved vaccines give the immune system some of the targets for the target practice. As the vaccines are tweaked to match the various epitopes as they evolve, scientists are watching the evolution of variants very closely. And, as time goes on, they will also be watching the performance of the different vaccine tweaks to the new variants that emerge with still more differences from the ancestral version of SARS-CoV2. That is why, not withstanding the variants that are always emerging, you should get whichever COVID-19 vaccine that is offered to you as soon as you are able. It is also why you should continue taking normal precautions that reduce spread of the virus, namely social distancing and masking.