By Aryan Weisenfeld
Vaccines And New Variants
As the vaccine rollout progresses and a new administration takes over, there is reason for great optimism these days. We hear reports of vaccine efficacy at or near 95%, yet there is no shortage of experts warning of potential issues, including new variants and antibody escape.
The problem is the communication of these issues is buried in technical jargon or incomplete analysis. Fortunately, since I’m always looking for new things to worry about, I spent some time curating these remarks and studies and will do my best to explain them in easily understandable ways.
This article will be lengthy, so the short version is this: there are unfavorable outcomes regarding the present vaccine, but they are unlikely and we should all be fine.
How the COVID-19 Vaccine Works
Let’s begin by talking a little about how the COVID-19 vaccine works, and what is meant by antibody escape. To understand how the vaccine works, we need to know the basics of how COVID enters the body. As shown in the figure in the tweet below, a human cell has a receptor wherein if the ‘spike’ protein of COVID attaches to it, it can penetrate the cell and enter the body.
The purpose of the vaccine, then, is to generate antibodies that can actually bind to the spike protein at a receptor binding domain that prevents the spike protein from attaching to the ACE2 receptor and entering our cells. Think of it as a COVID molecule, the antibody, and the ACE2 receptor as three Legos. If the antibody takes up all the open Lego pegs of the COVID molecule, it cannot attach to anything else.
Simple enough.
Potential Problems From New Strains
The problem with this is that if we think of the spike protein on a COVID molecule as a lock, and the antibody as a key, that key will only work on a certain configuration of lock. If the spike protein mutates – which occurs all the time in any type of virus – then those antibodies might be rendered ineffective because they can no longer bind to the spike protein. Though this happens regularly with viruses, it generally takes years, but there is evidence that it is happening at a rapid rate with COVID. When you read anything mentioning mutations at the E484K site, or specific mutations that give rise to the B.1.1.7 strain – this is what they mean. It’s not important to know specific nomenclature – just remember that mutations change how antibodies respond to a particular foreign substance.
Should We Be Worried?
Should we be worried then? The very unfortunate reality is that it depends markedly on who you ask. Of course the scientific community will always be divided on how to analyze research, but during a time where democratization of epidemiological information is so prevalent, and people get their news from Twitter, it does everyone a huge disservice when experts make authoritative or incendiary statements while completely ignoring the fundamental tenant of science: to analyze and find truth.
Example:
Twitter Epidemiology Confusion
There is a subset of the Twitter epidemiology cognoscenti (who in my opinion exist more to gain notoriety than to inform) that believes these mutations are a big deal, however their analysis is usually superficial at best. There is another subset that still recognizes that this could be a threat, but for a variety of reasons believes the current vaccines will be good enough to get us back to normal life, and that they can then be updated as necessary (like a flu shot).
Let’s walk to the edge of the cliff first, then come back to safety. Renowned public health expert and former Harvard Medical School / School of Public Health faculty, Dr. Eric Feigl-Ding is about as big of a doomsayer as there is on Twitter, and he believes the mutation concern is ‘very very real.’
South African Variant / Immune Escape Confusion
Feigl-Ding walks through how this South African variant might have several mutations that have complete immune escape, and how we should all be just so very concerned. However, buried in his eight tweet on this topic is the quote stating that despite all of this, this is not something we should be ‘horribly freaked out about.’ Further to this point, in a previous tweet (in which Dr. Feigl-Ding labels the findings ‘STUNNING’), in which he speaks of antibody escape and how a study from the Bloom Lab (more below from this lab when we discuss the non-catastrophizing group of scientists) shows that the new variants could produce a 10x reduction in neutralizing antibody ability, in the 9th tweet of the thread states that the vaccine should not be affected too much.
At this point in my research, I was feeling lost. Why is someone so prominent purporting doomsday scenarios and then flippantly saying we should not worry because it will not impact the vaccine too much? A 10-fold reduction sounds like a lot to me. Where is the nexus between this reduction and no impact on the vaccine?
Bloom Lab Clarifications
Fortunately, I had the Bloom Lab Twitter account to walk me back from the brink. I’ll post the entire thread below, but a short summary is even though mutations at specific sites, like E484K, reduce antibody binding and neutralization, it did not eliminate it. The vaccines, in what really is a scientific miracle, have such a high efficacy that even these types of neutralization reductions are not enough (right now anyway) to make the vaccines any less ‘good enough.’
Conclusion
I believe there are other reasons why the present vaccines will be efficacious against the present mutations, one of which being that antibody neutralization is just one immune response, but that is not terribly important. What is important is to put in perspective just how good the current vaccines are, and not to get disenchanted because the scientific community on Twitter uses the word ‘significantly’ in a different way that it is ordinarily used (i.e. a statistically significant reduction in antibody neutralization does not mean a meaningful reduction). Even if mutations present that do show a meaningful impact on vaccine response, we should be aware that these vaccines can be updated, and updated quickly.
Thanks for reading.
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