Stuff

“Glad you're back writing. Stinks about the hives. I experienced weird symptoms after my 3rd. shot. I was very hesitant to take the vaccine, but did, based on my age(65). Two years of observing the handling of covid by our government and public safety officials and some docs, has caused me to lose all faith in the system. Any idea why they're still pushing a vaccine that does not work as promised? Isn't it smarter to use the monoclonals and other therapeutics long before a patient gets in to the danger zone? Hard to know who and what to believe anymore.”

I have absolutely no clue why the feds are pushing for a vaccine they know doesn’t work or, at least, doesn’t work very well.

So, for the next question about monoclonal antibodies, I will give a brief lecture on virology, vaccines and antibodies. Each is an enormous topic or field, so please tolerate the simplifications.

Below is a now famous illustration from the CDC on what SARS-CoV-2 “looks” like. The red triangular sort of things are the S protein, better known as the Spike Protein. If these triangular red things look like they are made of three parts, that’s because they are. Three S proteins are come together as a homotrimer, meaning three of the same proteins making one larger protein.

As you all know, the Spike Protein binds to receptors on human cells and mediates entry. If a cell doesn’t have a receptor for the Spike Protein, that cell cannot be infected.

The mRNA vaccines are made of little detergent or soap bubbles, which contained the mRNA for the Spike Protein. M stands for messenger. In perhaps the coolest thing in Biology, Life worked at a code to make proteins. The code for a given protein is what we call a gene. In our cells, the gene is in DNA, and then from there, mRNA is copied, like a mirror image. The mRNA then goes out into the cell, meets up with some ribosomes, which interpret the mRNA’s code, and make proteins, which consist simply of varying numbers of 20 different amino acids. Every protein in Life is simply a chain of these 20 different amino acids.

Back to the mRNA vaccines, Pfizer’s and Moderna’s, each contains mRNA which encodes part of the Spike Protein. These liposomes or soap bubbles fuse with cells, like two bubbles fusing together in the summer when you blow bubbles. The mRNA then just floats around inside the cell until it finds some ribosomes, which then interpret the mRNA’s code and produce a shortened version of the Spike Protein. Our bodies recognize the Spike Protein as “non-self”, meaning the Spike Protein is shaped differently than any of the “self” proteins, those made by our cells.

So, the immune system only sees the Spike Protein. SARS-CoV-2 has many other proteins, but the vaccine only produces the Spike Protein. Therefore, the immune response is only against the Spike Protein.

Monoclonal antibodies – mAb (m for monoclonal and Ab for antibody) are powerful tools in the lab and in the clinic (meaning patient care). Many of the new, great cancer drugs are monoclonal antibodies. Ok, so what’s an antibody? About 5 or 6 pounds. Sorry. An antibody is the second coolest thing Life figured out. Antibodies are proteins we make against viruses, bacteria, vaccines, and toxins. When we given a vaccine made of one protein, as the mRNA vaccines are, then we make antibodies against that one protein. The human body makes antibodies which bind all over the Spike Protein. But viruses can be relatively resistant to antibodies, depending on where the antibody binds to the virus, kinda like the Death Star. Bombing the outside of the Death Star caused some damage, some explosions and maybe some screaming of the crew, but it didn’t affect the Death Star’s ability to kill planets. Red Leader’s Proton Torpedo missed the shaft, but Luke’s bomb, guided by good thoughts, located the shaft and KAPOW! Antibodies are like that – some slow the virus down very little and others neutralize the virus completely.

Antibodies bind to very small areas on the Spike Protein. A neutralizing monoclonal antibody is binds to an area critical for the virus entering a cell and neutralizes the virus, meaning it can’t infect a cell. Neutralizing mAb are found in the lab and then grown up in huge quantities for therapeutic use. A given mAb, however, works as long as mutations in the Spike Protein of that strain or variants do not affect the mAb’s binding site. If mutations do substantially affect a mAb’s binding site, kinda of like moving the shaft on the Death Star.

Variants – Viral variants are defined by mutations in the Spike Protein, which differ from the original or “ancestral” strain. So, Delta, Omicron, etc. are defined by the number of mutations in the Spike Protein compared to the “ancestral” Spike Protein”. SARS-CoV-2 makes several other proteins, which stay relatively unchanged compared with the Spike Protein, but variants are only defined by the changes in the Spike Protein.

Ok, so, what’s my point?

The mAb’s were designed to bind to the “ancestral” Spike Protein. So, when a variant gets mutations in the binding site for that mAb, that mAb cannot bind the virus any longer and cannot, of course, neutralize the virus.

The vaccines induce an immune response ONLY against the Spike Protein. The more mutations in the Spike Protein in a new variant, the less your immune response will against this variant. Vaccines induce many different antibodies, so the immune response to a Covid mRNA vaccine cannot as easily be affected as that of a mAb. However, the immune response induced by a mRNA vaccine is less and less effective as newer variants develop more and more Spike Protein mutations.

In short, the mAb and the antibodies, which our bodies make after mRNA vaccination, bind well to the “ancestral” SARS-CoV-2 strain, but as variants gather more and more mutations, their effectiveness decreases steadily.

Infection with SARS-CoV-2 induces even broader immunity against variants. SARS-CoV-2 produces at total of 16 different proteins. When infected with any virus, our bodies develop immune responses to all 16 proteins. The mutations in a variant are only in the Spike Protein. Therefore, the antibodies, which bind to one of these other viral proteins, still bind to the variants.

So, what to do?

We know antibody levels after vaccination correlate well with protection. For some reason, we are not using those levels to look for individuals who are not immunocompromised, but have declining levels of antibodies against SARS-CoV-2’s Spike Protein. Certainly, we can start checking antibody levels and, if low, consider getting boosted. And this has been done in transplant patients, who take medicines chronically to weaken their immune system on purpose. As result, they respond less well to vaccines.

Further, in addition to those with weak immune systems, we know risk factors for severe disease - obesity, diabetes, and age.

So, if you 65 or older and/or you have obesity or diabetes, then consider getting the first booster.

As for the fourth shot or second booster, the data just don’t support that yet for anyone. Compounding this issue is where are the vaccines against the variants? I have no idea. Why are we pushing a second booster of a vaccine based on the ancestral strain when the new variants have so many mutations in the Spike Protein? I still don’t know. I didn’t even think they were going to study the second booster using the vaccine based upon the ancestral strain.

The data from the pediatric vaccine trials give plenty of reason to doubt the efficacy of a second booster. The NY State Dept. of Health published on February 28th a preprint on vaccine efficacy (VE) in children 5-11 or 12-17.

https://www.medrxiv.org/content/10.1101/2022.02.25.22271454v1#p-5

The article states - “Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76% and by 28-34 days it was 56%. For children 5-11, VE against cases declined from 65% to 12% by 28-34 days.” [95% CI values removed from text]

This study was started in mid-December or just as omicron was arriving on our shores. VE in 5-11 yo kids at 2 weeks after the second dose was only 65%. But worse yet, at 4-5 weeks after the second dose, VE went down to 12%. We don’t use any vaccine with an efficacy that low.

So, for those who were pushing for young kids to get the Covid vaccine and, worse, those who supported mandating that 5-11 yo kids get the vaccine, what do they say now?

To quote “The History of Pi”, to live is to incur risk. Getting the second booster without first showing the person has low antibody titers against the Spike Protein, to me, seems reckless. We don’t even know if the vaccine-induced immune response is going to help against the newer variants, which have more mutations than omicron. Some people want to do something. But my resident once demanded of me as an intern that “Don’t just do something. Stand there!”. Yes, masks, boosters, rabbit’s feet, garlic necklaces…each is something to do. But only boosters mess with your immune system. If doing something helps you deal with your Covid anxiety, then get 10 boosters if you want. But if you want to make the most educated decision which gives you the least overall risk, consider the above.

So, I saw a couple of hundred more Covid pts in November – January. I made the decision not to get the booster. Remember, I knew I had a strong reaction to the second Covid vaccine dose, so I knew I had vaccine induced immunity. Then, the booster was forced on me just as Covid rates had plummeted.

In other words, I had just gone through the highest risk period of pretty much any human ever and I did so without getting the booster. And yes, I took off my mask in Covid pts’ rooms. None of this was bravado; my decisions were based on my understanding of the vaccine data and the mask data. Then, after this huge spike was over and my exposure to Covid pts was close to zero, I was forced to get the booster, from which I got an adverse effect. For the cynics, during this period, I got tested 3-4 times to attend events or for travel and was negative each time.

I think one’s decision on a second booster comes down how you answer this question –

Do you still wear a mask in situations where you don’t have to?

If yes, then get the second booster.

SMS