Attacking the Spike Protein

The idea embraced by most of the current effective coronavirus vaccines is to teach the body’s own immune system, notably your T-cells (actually CD8+ T-cells), to identify a COVID-19 intruder instantly and attack it. Because of the virus’ unique look, those telltale spikes that sit around the corona of the virus, effectively most of these vaccines simply provide a look-a-like but non-toxic manufactured COVID-like “shape” for the T-cells to sense (i.e., genetic “instructions”). Think of it as T-cell show and tell. The injections give the T-cells enough time to learn what to do. Without that learning curve, the virus otherwise has time to get into the body and use our own organs to replicate that deadly and most uninvited visitor. The second shot, where required, is literally a completion of the lesson, and tests show that the immunization lasts much longer with that second shot: more “educated” T-cells resulting from that second shot. There are more than 60 other vaccines around the world at varying stages of development. Let’s look at the major vaccines in use.

Moderna and PfizerBioNTech use a manufactured mimicking protein – messenger ribonucleic acid (mRNA) as the carrier of that spike protein shape. Using CRISPR (a fantastic genomic editing process), that spike shape identifier is edited into the man-made mRNA and contains no version of the virus, dead or alive. AstraZenca uses a similar approach, but its two-shot protocol uses a dead flu virus as the shape carrier. COVID-19 vaccines made by Novavax and Johnson & Johnson also focus on the spike proteins. And while the J&J is currently being administered in a one-shot regimen, researchers are looking at a potential improvement if a two-shot process were used.

“Johnson & Johnson’s vaccine works in a similar way [to Moderna and Pfizer], but stores the genetic instructions in DNA instead. The gene is inserted in a modified cold virus called an adenovirus. The company used the same approach to make its new Ebola vaccine… Because DNA isn’t as fragile as RNA, and the adenovirus around it provides extra protection.” Adele Peters writing for the March 1st FastCompany.com. J&J has also joined forces with pharma giant, Merck (principal architect of the Human Genome Project), to ramp up production of their vaccine.

Melissa Healy, writing in the March 2nd Los Angeles Times, adds: “The two doses of Russia’s Sputnik V COVID-19 vaccine use two kinds of viruses to transport the genetic instructions that tell the immune system which coronavirus surface proteins to look for. The first is a harmless cold virus. For the second shot that comes 21 days later, scientists engineered another innocuous cold virus to carry the cargo. This way, there’s no chance the immune system will inadvertently attack the harmless cold virus when it’s time for the second dose. With a new ride, the vaccine’s genetic payload can slip by unchallenged.”

The problem that has surfaced is where a first shot of a two-shot regimen is administered but where the availability of the same vaccine for a timely administration of that second shot just cannot be met. A short time delay may still allow more time to get that second shot, but there are two big questions impacting the vaccine researchers today: first, how to address vaccine resistant variants and second, whether you can mix a vaccine from one regimen (the first shot) with a vaccine from an entirely different regimen?

Clearly, as the virus mutates, adjusting vaccines or designing booster shots becomes inevitable until the requisite herd immunity kicks in. The virus has mutated thousands of times already, but most of these variants are not materially different and have little or no impact on those who have been immunized. The good news is that once a truly vaccine resistant variant is genetically mapped and modeled, it is a matter of days to create a viable adjusted or booster vaccine; the rest of the time is clinical testing, which can be accelerated. The other good news is that none of these major vaccines has any impact on altering human genes, and the number of severe allergic reactions to these inoculations is exceptionally low. 

Sorry vaccine skeptics and anti-vaxxers, there is zero evidence that these vaccines carry big risks. And yes, you may face a strong reaction to the second dose, but a) it will be gone within a day or two, and b) that reaction only shows it’s working. Better that risking PASC (long tail) complications that have surfaced in a very sizeable number of people who have suffered through and recovered from a COVID infection, even mild infections. Or face a severe and often deadly case of the virus itself. Just remember the hard numbers of infections and deaths!

But the mix and match question is intriguing. Given shortages, sooner or later, mismatched vaccines will happen. Some folks might not even remember what they got the first time around. If there is a mix and match, perhaps, the researchers posited, the first shot would have been a waste and their might be negative from adding that second, but different, vaccine. Or maybe, the results could work even better, even addressing some of the resistant virus variants that have surfaced. 

“‘I wouldn’t make any changes unless you’ve got good data,’ said Dr. Anthony Fauci , director the U.S. National Institute of Allergy and Infectious Diseases. ‘I don’t think you mix and match without results showing it’s very effective and safe.’… Now British researchers are trying to do just that.

“Last month, a team of vaccinologists from Oxford University began recruiting 800 or so people ages 50 or older for a complex study to see whether vaccine switching could work… Using an eight-armed clinical trial, they’ll test regimens using various combinations and intervals of the two vaccines currently being dispensed in Britain: one made by Pfizer and BioNTech and another developed by Oxford and AstraZeneca.

“In announcing the mix-and-match vaccine trial, Dr. Matthew Snape cited experiments in mice in which combinations of the Pfizer and AstraZeneca vaccines boosted immunity better than two doses of either one alone. Perhaps it would work in humans as well.

“Both vaccines prime the immune system to target the spike protein on the surface of the coronavirus, which plays an instrumental role in the infection process. But the vaccines home in on different parts of the spike, and they deliver their payloads by very different means.” Healy

The big picture view of all of this is the entirely new approach (this pandemic is the first widespread test) based on teaching CD8+ T-cells what to look for by introducing non-toxic “shape” instructions so the body itself can destroy the invaders. CRISPR was the key, but the potential for containing future epidemics and finding new potential in cancer research are both staggeringly interesting and compelling. We just have to get the entire world on the same page to identify nascent infectious agents early enough to isolate the intruders and prepare required vaccines on a prompt and timely basis.

I’m Peter Dekom, and for those with an opportunity to get the vaccine sooner than later, with millions and millions of people who have already gone through that process as evidence of the safety of these inoculations, GET THE VACCINE!