One-Third of U.S. Troops Have Declined Covid Vaccine, Pentagon Says

@Quantum Nerd,@CenterField

Since my posts are often misunderstood I’ll preface my remarks by saying I see no current evidence of danger or undue risk from any mainstream Covid vaccine.


Now, on to what we just don’t know in relation to what we do know.

We know natural infections present more numerous specific antigens than the mRNA vaccines do as they are tailored to the S proteins specifically. This is very good at producing clones of neutralizing antibodies and T and B cell memory to this antigen. This approach is obviously working to prevent infection and lessen severity of disease. (Hopefully it’s politically correct to admit vaccines prevent infection now LOL).

Antibody clones in natural infection are much more numerous after natural infection. These include neutralizing antibodies to the N protein as well as massive numbers of non neutralizing antibodies. Also, there will be T and B cell memory developed to recognize antigen from natural infection not presented by the mRNA vaccines.

Is this meaningful? We don’t know. We do know we are very ignorant on positive and negative feedback loops involving cytokines, antibody titers, T cell concentrations, etc. We only know enough to realize how much we have yet to learn.


We know we have a history of oversimplification and sometimes even dismissal of things we don’t understand when it comes to physiology. “Vestigial” organs such as the appendix for example. Epithelial cell regulatory functions we didn’t look for initially because we assumed they couldn’t have any.

So, is it possible the body has a very good “reason” to produce antibodies and T/B cell memory to antigens that are not directly tied to cell entrance by the virus? Absolutely. I won’t speculate too much here, but I don’t think it’s outrageous to assume there are immune response regulation feedback loops dependent on these “unnecessary” (not unnecessary literally, we already know they have some functions) cohorts of antibodies.

In my opinion it’s unlikely receiving an mRNA vaccination to one or even a few pathogens would negatively impact the immune system. But in the case where all vaccinations specifically target only one antigen of each pathogen and result in no other antibody or humoral immune system components I don’t think it’s inconceivable we may create an imbalance resulting in disruption of feedback loops involving these components.

Again, I’m not being critical of the technology. I’m a fan. I’m just pointing out there are “scientific” reasons to be cautious and not all caution is nutbaggery.

 

I don't think so. The allergic reactions last I checked were occurring in a frequency of 11 out of 1,000,000 doses for Pfizer and 3 out of 1,000,000 doses for Moderna. That's very small odds. And nobody who had an allergic reaction, died from it or suffered permanent consequences. The virus is much worse than that. So even for Pfizer, this is 1 in 91,000 while the virus kills 1 in 100 to 1 in 50 (1% to 2%) and maims 1 in 10 to 1 in 5 (10% to 20% showing up with long-term consequences such as brain fog, pulmonary fibrosis, chronic heart inflammation). There is no doubt that the vaccine is way way way safer than catching the virus.

 

557, what makes you say that the mRNA vaccines do not produce T/B cell responses?
Both the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine stimulate T cell responses in addition to B cell responses (Sahin, July 2020; Anderson, December 2020). 
https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1
"Most participants had TH1 skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon (IFN)γ was produced by a high fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T-cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest multiple beneficial mechanisms with potential to protect against COVID-19."
https://www.nejm.org/doi/full/10.1056/NEJMoa2028436
"In response to S-specific peptide pools, the vaccine elicited a strong CD4 cytokine response involving type 1 helper T (Th1) cells among participants in the two age subgroups who received the 100-μg dose and among participants between the ages of 56 and 70 years who received the 25-μg dose"
Both these vaccines have elicited both binding and neutralizing antibodies in titers higher than the natural infection, which is one of the reasons why it is recommended that even people who have had the natural infection, are offered and accept the mRNA vaccines. T cell responses will create T cell memory and subsequent B cell activation. I don't see much of the imbalance you're talking about.
Now, if you only meant that the vaccines don't produce T and B cell responses against the N protein antigen, then you are correct.
There is a reason why the vaccines target the S protein: it is the virus' Achilles Heal.
This is exactly why these mRNA vaccines are more immunogenic than the CoronaVac, for example, which is a vaccine made with whole inactivated SARS-CoV-2.

 

excellent point about the virus also making mRNA!
Still, facts won't dissuade conspiracy theorists, as you know.

 

Yes, mRNA vaccines produce non neutralizing and neutralizing antibodies against the S protein antigen as well as T/B memory to that antigen. But only that antigen. There are no antibodies or T/B memory to the N antigen.

And yes, specifically targeting the S protein is great for preventing infection and reducing severity of disease from infections. My point is there may be consequences to not having accompanying antibodies or T/B memory to other antigens presented by SARS-CoV-2 besides the spike antigen.

We simply don’t know all the functions of these vast cohorts of antibodies and memory cells that occur in natural infections and to a lesser whole virus vaccines. To assume they are benign and don’t help regulate the entire body’s immune responses to other pathogens going forward is naive.

 

I find it funny when they enlisted they had no opinion!....They lined up and got all kinds of shots....Military can easily say, everyone gets vaccinated....No asking, no please, just line up!

 

Not every antigen is a good antigen. For example, protein fold is important, as is protein size, and amino acid composition. Large numbers of polar and charged amino acids in the sequence make for a better antigen than non-polar sequences. That's why membrane proteins aren't great antigens, and when antibodies are raised against them, people usually use random coil sequences in the N or C-terminus (the water-exposed parts).

Out of the 29 covid proteins, the spike protein is the most exposed on the surface, that's probably why it was chosen as the antigen for the vaccine. The M protein might have been another target, but the N protein resides inside the envelope, and would only be accessible to anitbodies after the disassembly of the virus.

I am not a covid expert, but these are my guesses why the S protein was chosen as the antigen, rather than M or N.

Here is an overview explaining antigen properties and immunogenicity:

https://mainebiotechnology.com/antigen-design-considering-target/

 

One thing I've heard recently from a vaccine concerned friend of mine is that taking the current vaccine can leave you open to ADE if you then get the P variant or any others which are resistant to the vaccine.
I've tried reading up on it but am not really equipped to understand the papers.
The abstracts seems comforting but words like ''unlikely'' are a little off-putting.

https://pubmed.ncbi.nlm.nih.gov/32785649/

 

"Unlikely" is just scientist speak. In a paper, you can't say "impossible", because nothing is impossible, scientifically speaking. A little bit stronger verbiage would have been "highly unlikely". Not sure why that wasn't used.

 

I've reluctantly addressed ADE here, several months ago. @557 practically forced me to do it, as he was correctly turned off by my refusal to divulge the less charming aspects of vaccines, given that I was afraid that people would then not accept the Covid-19 vaccine and many would die due to this lack of acceptance. So, yes, it is a theoretical possibility... but in real life we haven't seen it. Sure, the vaccines have been with us for a short time. So it's not impossible. But like your article correctly proposed, it is unlikely. I wouldn't be upset with the language used. Scientific papers authored by good scientists never want to be bombastic, so we choose sober and restrained language (Quantum Nerd, also a scientist, gave you the same opinion above). The take-home point is that the SARS-CoV-2 is much less likely to provoke ADE than some other pathogens.

 

The spike attaches to ACE2 receptors like a key into a door lock, and enables the virus to penetrate the cell. It is a very efficient target for vaccine-induced antibodies because of its location (on the virus' surface) and function. If you knock down the virus' ability to bind to the ACE2 receptor by attaching antibodies to the S protein, that will then result in the S+Antibody complex not fitting the receptor (wrong key; too big for the keyhole), then the virus can't infect the cells, therefore can't replicate.

 

Yes, I realize that. I was thinking about this from the biophysics point of view. Why not use covid proteins other than S as antigens? Because they have poor accessibility to the antibodies. Even if some of the proteins released in the cytosol during replication could be blocked by antibodies, the antibodies do not get there. Therefore, the ONLY proteins that really make sense as antigens are the S and the M protein. It would be interesting to look at antibodies from recovered covid patients to see which of the 29 proteins their antibodies target. This probably has been done already, although I am not aware of it (again, I am not a virologist).

Actually, after looking it up, T-cells against other corona viruses also target other covid proteins, including M an N, as well as replicases. This makes sense, since the T-cells respond to dendritic cells that display antigens from cells they have digested on their surface, which can include intracellular antigens. I have to admit that immunology is one of my weaknesses in science (maybe not surprising as a chemist), so I am learning a lot researching this.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123234/

 

I don’t disagree with any of that. My point here is we don’t know if something we consider a “not good” antigen induces production of T/B cells or antibodies that are involved in feedback loops regulating immune response.

Just because in SARS-CoV-2 the spike is most important (from a vaccine perspective) because it’s involved directly with entering host cells doesn’t mean antibodies production or cellular response to other antigens doesn’t play a role in regulation of current or future infections.

I’m not saying this is a problem with mRNA vaccines, I’m just trying to make sure we don’t make assumptions that set us back—like assuming endothelial cells didn’t have regulatory functions.

That was a good link. I’d encourage anyone interested in this discussion to read it.

 

When @CenterField and I have discussed this in the past, there really never has been any evidence it’s happened or will happen. It’s just theoretical. Many months have passed and still there is no evidence it will be a problem. With many convalescents having been vaccinated and many vaccinated having been exposed to natural infection, as well as monoclonal antibody and convalescent antibody treatments being used, by now we would almost certainly have some evidence ADE was going to be a player in Covid.

I think the ADE excuse for refusing vaccination at this point is just that, an excuse—not a reason.

 

~ Interesting that so many are declining the vaccines. People who are younger and fit likely do not need the vaccine. If you have risk factors ( obesity etc ) that's a different story.

~ It could be happening now.

 

That's comforting although it wasn't going to dissuade me from getting vaccinated (I'm booked in for next Friday) and I don't think anything will convince my friend to change his mind.
I have two friends who are anti-vaccine and both suffer from ''a little knowledge is a dangerous thing''. They are both well read but IMO read the wrong things. The guy who brought up ADE is convinced that regular consumption of coconut oil will keep him safe from all illness.

 

I’ve met coconut oil “aficionados” myself. LOL. In fact, I know a few folks who think it’s melaleuca oil one day, gogi berries the next, and coconut or something else next year.

Glad your number is up for vaccination. I’m happy for you!

 

Yes it's great news. We are in fact ahead of schedule in the UK. Over 50s like myself were due to get our first jabs by mid April but most people that I know of my age have already had it or at least got a date.

 

A date to dance with the needle.
I am very happy for you. I already have both my Nano Chips. In a week I should be at 95%.
Just waiting for that USB port to grow out of me ars.

hihihihihihi

 

Honestly, those people who use their phones to Tweet about tracker chips in the vaccine are just doing their bit to strengthen the gene pool by refusing to get inoculated.

 

OK, so, a bit of cell and humoral immunology primer here:

Yes, exactly, dendritic cells present the antigens to T cells and those are fragments of all sorts (S, M, N, and E proteins, primarily - these stand for Spike, Membrane, Nucleocapsid, and Envelope and all four make what we call structural proteins; the virus also has nonstructural and accessory proteins, adding to a total of 29 proteins; other than the four structural ones, important ones include the virus' main protease, and its RNA polymerase).

Dendritic cells are called APC or professional APC (antigen-presenting cells) and when they present these proteins on their surfaces, the naïve or resting T cells become activated. They also produce cytokines that activate B cells and promote their differentiation. Dendritic cells are present in entry points for viruses, like the skin (where they are called Langerhans cells), and the linings of the nose, lungs, stomach, and intestines. Once activated they migrate to lymphatic tissues to interact with the T and B cells.

Another APC is the macrophage. Together with monocytes and dendritic cells, they make the MPS, or mononuclear phagocyte system.

Once the APCs activate the naïve T cells, they differentiate into cytotoxic T cells (CD8+) and helper T cells (CD4+).

Explaining what CD8 receptors are: they are co-receptors that develop on the surface of a cytotoxic T cell, and combine with T cell receptors and with MHC class proteins (Major Histocompatibility Complex molecules) presented by the other cells, to form a bridge that recognizes other cells that are infected with a pathogen or are cancerous. Once that bridge is established, the T cell recognizes the infected (or cancerous) cell as such, and the receptors generate a signal that makes the T cell release cytotoxic molecules that kill the infected or cancerous cells.

And what about CD4? These are different co-receptors, which characterize the T cell as "helper", that is, it helps other cells. Now, the CD4 co-receptor interacts with a T cell receptor and MHC class II proteins. This allows the T cell to recognize pathogenic peptides. Once the T cells recognize the antigen, they differentiate into 3 main types: TH1, TH2, and TH17. TH1 cells help activate macrophages and cytotoxic T cells. TH2 activate B cells. TH17 cells recruit neutrophils and macrophages.

There is a third kind of T cells, called regulatory or Treg cells. They also have CD4 receptors but they do not activate other cells. What they do is, they shut off the immune system when it's no longer needed. They produce anti-inflammatory cytokines, they kill activated T immune cells (crazy, isn't it?) and inhibit dendritic cells so that they can't activate more T cells.

CD stands for clusters of differentiation.

People hear about CD4 and CD8 but there are many CDs. B cells have many different ones. CD19 through CD24, and CD40, CD72, CD79, CD80, and CD86 are the most important ones. Each one characterizes a different subtype of B cells which have all sorts of functions and maturity levels. For example, different subtypes are responsible for antibody production (natural, adaptive, or auto), cytokine production (IL6, IL10, IFN-y, etc. - these are helpful but if they are upregulated a.k.a. a storm, they can do more harm than good), lymphoid tissue organogenesis, transplant rejection, wound healing, dendritic cell regulation, Th1/Th2 cytokine balance, B cell-T cell co-stimulation, and tumor immunity. Maturity levels will include naïve, activated, memory, and plasma cells (the antibody factories).

B cells are the ones that can go bad and proliferate into lymphomas and leukemias.

B cells are found in several locations: the bone marrow, the spleen, the liver, the thyme, lymph nodes, circulating blood, and other places. B cells are extremely complex, more than T cells. I'd have to spend a lot more time going into each subtype, but I think I'll stop here because this is not the level of detail that most readers here would be interested in.

One detail that I forgot to mention when you asked why the S protein is the target of the mRNA vaccines: the S protein is the one that fosters neutralizing antibodies. Neutralizing antibodies are those that not only bind to a virus, but they do so in a way that prevents the virus from being infectious. They do it by one of two mechanisms: either they block interactions with the receptor that will give entry to the cell (the case of the S-protein-neutralizing antibodies for the SARS-CoV-2), or they attach to the capsid (which is around the genome) in a manner that inhibits uncoating of the viral genome. Only a subset of the various antibodies that bind to a virus are capable of neutralization. The others are called binding antibodies and do not influence infectivity, and are less able to reduce viral burden.

 

They are giving you the choice because the vaccines are still under EUA (emergency use authorization) and are not fully approved. Typically, treatments under EUA are not mandatory.
But you are mistaken in thinking that Covid-19 is of no consequence for young people. There are many young people showing up with sequelae (that is, organ damage following an infection by an aggressive virus) such as brain fog, chronic fatigue syndrome, lung fibrosis with permanent shortness of breath, and inflammation of the heart that can lead to premature heart failure. You're playing with fire by thinking "why bother." Yes, the reason to bother, is to avoid potentially a curtailed life and a lifetime of problems, even if you don't die from the acute phase of this illness. The percentage of young people with sequelae is at least 10% (1 in 10) up to 20% (1 in 5). Yes, you should all take the vaccine which is much much safer than the disease itself, in terms of long-term problems.

My problem with this is not some accusation of you guys being selfish or something. It is my concern for your health. I love our military and I want you guys to be protected and to do well. Please pass this on to your brothers and sisters in arms. You guys should look at a study by the Ohio State University looking at college athletes who had Covid-19, many of whom had no symptoms whatsoever and recovered from the acute phase without dying (it is very rare that Covid-19 kills young people although it dos happen on occasion), 30% of these athletes had cellular heart damage and 15% of them, inflammation of the heart (myocarditis). Not fun. Don't underestimate this virus, please.

https://www.fox2detroit.com/news/oh...athletes-have-heart-damage-linked-to-covid-19

https://jamanetwork.com/journals/ja...ign=ftm_links&utm_content=tfl&utm_term=091120