The Virus and the Vaccine

[roger001]

Well...I personally think the virus and the mess it has created for us and NCL is pretty cruise related.  You may not think so and delete if you wish.  But, I just read the following, a lengthy article written by a Doctor at Vanderbilt who specializes in immunology. He wrote it down to a level that even an idiot like me can follow.  Now...you can certainly say, what does he actually know...I'm going to decide the value of the vaccine myself.  For me, I've got to rely on folks like the doctor, because as a retired air traffic controller, I just flat out don't have the medical background to outguess the medical folks.  Anyhow, here's the article.  No politics here, just the facts Jack as told by a doctor.  Delete if you wish.  By the way, one of our Tennessee gals, Dolly Parton, gave Vanderbilt one million dollars for vaccine development.  Way to go Dolly!  

 

How Does an mRNA Vaccine Against COVID Work?

I have been getting or seeing this question a lot on the socials, so I thought I would take a minute to explain it. The Pfizer/BioNTech and Moderna COVID-19 vaccines both fall into this category. A lot of folks have been simultaneously impressed and also made a little bit nervous by the speed with which these vaccines have been able to come from the drawing board to the forefront, and both of those feelings are totally understandable.

The first thing that I want to say is: Rapid vaccine development is not as new as it has been hyped to be by some folks. Every single year, vaccine developers make a flu vaccine from scratch to try and tackle the flu. The reason they do this is because influenza is a 90 mile-an-hour-train-wreck of a virus. It is constantly falling apart with genetic mutations and rebuilding itself. That’s why as it circulates seasonally around the world it can start out as one strain of influenza virus and then become another strain of influenza by the time it gets back to where it started the next winter. A lot of really amazing basic science has made it possible for us to not only understand the influenza virus, but also to rapidly make a safe vaccine for it every year.

Similarly, the field of vaccine science was able to safely test, advance, and deploy an Ebola vaccine in a very short time in 2014, thanks to decades of basic science work that had been done to get ready for the big moment of need.

COVID-19 is similar, except it isn't nearly as unstable as influenza. After the original SARS outbreak in 2003, basic science research in coronaviruses was undertaken to understand how they enter the body and cause disease. (side note: if you don’t already know, SARS-CoV2 AKA the virus that causes COVID-19 disease, is similar to another coronavirus that caused the SARS outbreak in 2003.) The protein that is important for this type of virus to attach to our bodies, the spike protein, was identified. For most viruses, your immune system will ultimately try to figure out a way to prevent the virus from entering the body by blocking its attachment to your body’s cells. Our immune system’s ability to block the coronavirus spike protein from attaching to our body’s cells using antibodies was identified as a potential pathway to becoming immune to coronaviruses. We therefore had a little bit of a headstart on COVID, for which a lot of scientists will deserve some credit when this thing is all over.

Now that we've established that rapid vaccine development isn't actually so new, rapid, or scary, I want to provide a brief explanation of how vaccines work. The most crucial thing is identifying which molecule on the virus or bacteria might be the one to make a person immune, such as the spike protein on the coronavirus.

Once a target protein that might make someone immune, such as the spike protein of SARS-CoV-2, is identified, you have to figure out how to get the immune system to recognize it and attack it both now and in the future using a vaccine. There are two steps that have to occur in the immune system in order for this to happen. The first step is a “Wake-up!” signal. The second step is a “Pay Attention and Remember This!” signal.

For most natural infections, the “Wake-up!” signal is little bits of virus or bacteria that your body automatically recognizes because of receptors that are handed down through our genes. When these molecular patterns (bits of virus RNA, DNA, toxins, bacterial proteins) are recognized, cells in your body secrete chemicals called cytokines to wake up the rest of the immune system and summon it to the place where the infection is happening, kind of like calling for the army using a radio.

The “Pay Attention and Remember This!” step is then carried out by a choreographed dance of specialized immune cells. Scouts such as dendritic cells and macrophages will capture and chew up the invading virus or bacteria into little bits. These little bits are then carried to lymph nodes where they are shared with T cells and B cells. In the presence of a scout who has been activated by the “Wake-up!” signals, the T cells and B cells will crowd around to see what is going on. The scouts will then present the proteins that they have captured, and just like in Cinderella, there will be one T cell and one B cell for whom that particular protein fits their specialized receptor the best. This T cell and B cell will then partner off and start encouraging one another to divide rapidly into many additional cells and to improve their ability to capture and clear the protein that was shared with them. As they do, their children will then exit the lymph node. The B cells and their children will start pumping out antibodies that are specific and able to attach to the infection. The T cells and their children will go to the site of infection, wherever it is, to lead the rest of the immune system as the lieutenants in the army, providing instructions on how to hunt down and eradicate the enemy.

(Side note: I LOVE immunology. It’s so cool!)

So, the next question is: what is mRNA?

mRNA (short for messenger RNA) is a small bit of genetic material that serves as a protein blueprint. Our bodies make a large amount of newly synthesized proteins every day using tiny little factories called ribosomes, that are found in a cell’s cytoplasm. In order to make those proteins, the nucleus of a cell creates mRNA to tell the ribosomes what proteins to make. These mRNA are then fed like a ticker tape through a ribosome as it synthesizes the corresponding protein using sequential amino acids.

Viruses and bacteria also use mRNA to make their proteins, but their mRNA are slightly different from ours in terms of chemical structure. Hence, an mRNA from a virus can serve as a “Wake-up!” signal that our bodies identify as a reason to summon the immune system.

The interesting thing is that an mRNA from a virus has to use the machinery of the human cell that it attacks in order to assemble a virus protein. Viruses work by taking over a human cell, and then forcing its ribosomes to make viral proteins and forcing the rest of the cell to assemble the viruses and spew them out. During that process, your immune system will eventually recognize that the cell is infected, and kill it, to shut down the virus factory.

However, a single piece of mRNA is not a virus. All it can do is to cause your body to make one single protein, and, if it is a viral mRNA, to wake up the immune system. It also doesn’t last very long, because it is degraded rapidly into component molecules. So it’s like a message that is automatically deleted after a very short time. It won't hang around in your body doing anything other than make a small amount of the spike protein for your immune system.

Hence, the way that an mRNA vaccine for SARS-CoV2 (COVID-19) works is like this. The mRNA is introduced into the body in tiny little bubbles that help it enter your body’s cells. Your cells simultaneously recognize that the mRNA is not supposed to be there and send the “Wake-up!” signal, at the same time that the ribosomes in that cell are making the spike protein and releasing it. Your scouts get the “Wake-up!” signal and come on patrol, where they encounter and sweep up the spike protein, and take it to the T cells and B cells in the lymph node. Then, the T cells and B cells become cells that are able to “Remember!” and rapidly make antibodies and a response against the spike protein.

That way, when you get exposed to the real virus, your antibodies are already able to mostly prevent it from entering your body. Even if it does get into your body, your T cells are already able to hunt it down and destroy it, anywhere, to prevent you from having a severe case. All that, and you never had to be exposed to the actual virus itself.

In Star Wars terminology, an mRNA vaccine works by providing your immune system with the plans to the Death Star's weakness, and it also gives your immune system the weapons you need to destroy it in case it shows up in your system. You don't even have to fight the first Death Star in order to defeat a second one.

Pretty cool, right? C’mon, you know it is!

In a nutshell, that's the idea behind an mRNA vaccine and how it is supposed to work. As an immunologist, this concept does not frighten me at all. It actually makes me pretty excited, especially in the middle of a pandemic. However, as I write this, the key thing is that these vaccines also appear to ACTUALLY WORK incredibly well, which is SO much more important, AND they appear to be safe as well. The FDA is reviewing the safety data as we speak, to determine whether to grant these vaccines emergency approval.

I’m withholding my final judgment until I see the safety data, but I have pretty high hopes that these vaccines are not only efficacious, but also safe. So that’s why I wrote this little piece, in order that we could all understand these vaccines a little better, since I'm planning to get one and I hope that you will too.

May this little article simultaneously inform and encourage you, therefore. I am really hopeful that we are about to enter a new phase of this pandemic soon, which I will happily dub “Episode VI: Return of our Immunity.”

11

 

[goldmom]

Thank you for posting this.  Very interesting read.

 

[Trimone]

Thank you roger001

[BermudaBound2014]

 

I agree with the Dr. I'm withholding my final judgement until I see the safety data.  

[Turtles06]

3 hours ago, roger001 said:

But, I just read the following, a lengthy article written by a Doctor at Vanderbilt who specializes in immunology.

 

Roger, I appreciate your posting what the Doctor wrote, but could you please provide the link and the Doctor's name.   Thank you.

 

[roger001]

23 minutes ago, Turtles06 said:

 

Roger, I appreciate your posting what the Doctor wrote, but could you please provide the link and the Doctor's name.   Thank you.

 

Sorry.  I can't do that.  It came from FB.  I'm not on FB.  However, my wife wanted to show me something on her FB account this morning.  As I looked, I saw this posted also by one of her "friends".  All I remember is that the preface said it was written by a Vanderbilt Immunologist.  If there was a name, I don't remember it.  I went back on her FB just now.  Unfortunately, her one billion or so "friends" have continued to post since then.  I scrolled for several minutes but did not run across that posting again.  If I see it again, I'm pay attention better.  I Googled the topic but did not find anything.  

[roger001]

10 minutes ago, roger001 said:

Sorry.  I can't do that.  It came from FB.  I'm not on FB.  However, my wife wanted to show me something on her FB account this morning.  As I looked, I saw this posted also by one of her "friends".  All I remember is that the preface said it was written by a Vanderbilt Immunologist.  If there was a name, I don't remember it.  I went back on her FB just now.  Unfortunately, her one billion or so "friends" have continued to post since then.  I scrolled for several minutes but did not run across that posting again.  If I see it again, I'm pay attention better.  I Googled the topic but did not find anything.                     I think I just lucked out.  I scrolled through some of the Vanderbilt staff and doctors (of which there are many).  I strictly by luck saw this Dr's name.  I'm pretty sure that was it...and he has immunology listed as one of his specialties.  

Cosby A. Stone  MD, MPH  

Allergy and Immunology

[nomad098]

A very good article explaining the basics of mRNA technology for those with no knowledge of the subject.

However because of its simplicity it glosses over some major issues with the technology, 

 it also glosses over the fact it took 9 years to produce the first flu vaccine. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains they don't make a new vaccine from scratch.https://www.medscape.com/viewarticle/812621

Ebola research has been going on for decades and candidates ready for testing before the outbreak in 2014. https://www.statnews.com/2020/01/07/inside-story-scientists-produced-world-first-ebola-vaccine/

The more times I read the good Dr puff piece the more holes I find in it 

I like the good Dr will be withholding my final judgment until I see the safety data from long term studies.

 

[mianmike]

26 minutes ago, nomad098 said:

 

  . . . it also glosses over the fact it took 9 years to produce the first flu vaccine. 

 

Huh????   So many advances have been made since the first flu shot.  The rate of scientific advancement is not static.  As technology and knowledge increase the rate of scientific advances speed up as well.   i.e. Moore's law

[nomad098]

5 minutes ago, mianmike said:

Huh????   So many advances have been made since the first flu shot.  The rate of scientific advancement is not static.  As technology and knowledge increase the rate of scientific advances speed up as well.   i.e. Moore's law

 

Actually the first flu shot was quite quick, science may have sped up but regulatory requirements have not until covid-19. 

https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation

 

I knew Moore's law was considered flawed a few years ago but apparently Moore's law is dead according to CEO Nvidia

https://www.cnet.com/news/moores-law-is-dead-nvidias-ceo-jensen-huang-says-at-ces-2019/

 

Personally I don't think it is just yet

[mianmike]

4 hours ago, nomad098 said:

 

Actually the first flu shot was quite quick, science may have sped up but regulatory requirements have not until covid-19. 

https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation

 

Personally I don't think it is just yet

 

I read the linked article and I don't see where the current covid vaccine approval process has been subverted or truncated.  Am I missing something? 

[Formula280SS]

A little snag, timing 50% delayed for end of year projection.

 

https://www.bnnbloomberg.ca/pfizer-declines-on-report-of-smaller-covid-19-vaccine-rollout-1.1531501

 

Pfizer declines on report of smaller COVID-19 vaccine rollout

[hamrag]

1 hour ago, Formula280SS said:

A little snag, timing 50% delayed for end of year projection.

 

https://www.bnnbloomberg.ca/pfizer-declines-on-report-of-smaller-covid-19-vaccine-rollout-1.1531501

 

This reported delay is not impacting the UK....our 40M doses are already in transit, according to local news outlets! 😉

[nomad098]

12 hours ago, mianmike said:

 

I read the linked article and I don't see where the current covid vaccine approval process has been subverted or truncated.  Am I missing something? 

 

Nothing has been subverted but trials have been truncated leaving 3 main questions

 

Will it break transmission?

What is the vaccines long term safety profile?

How long will effectiveness last?

 

If the process had not been truncated we would have probably had these questions answered long  before distribution. 

 

https://www.bbc.co.uk/news/health-55056016

 

 

[Formula280SS]

2 hours ago, hamrag said:

 

This reported delay is not impacting the UK....our 40M doses are already in transit, according to local news outlets! 😉

 

OK, sure "your" 40M doses are already in transit.

 

LOL.

 

You really need to take at least a minimal time effort to read and comprehend before boasting and certainly posting and not hoping for a jammy.  It gets old dealing with replies to the willing uninformed.

 

https://www.cnbc.com/2020/12/03/how-the-uk-will-roll-out-the-covid-vaccine.html

 

When will people get vaccinated?

 

The U.K. pre-ordered 40 million doses of Pfizer and BioNTech’s vaccine — enough to vaccinate 20 million people — but the delivery won’t be fulfilled all at once.

“The delivery of the 40 million doses will occur throughout 2020 and 2021, in stages, to ensure an equitable allocation of vaccines across the geographies with executed contracts,” Pfizer said on Wednesday.

 

“Now that the vaccine is authorized in the U.K., the companies will take immediate action to begin the delivery of vaccine doses. The first doses are expected to arrive in the U.K. in the coming days, with complete delivery fulfilment expected in 2021.”

Health Secretary Hancock told the U.K.’s House of Commons on Wednesday that each batch of the vaccine would be tested for safety. “I can confirm batch testing has been completed this morning for the first deployment of 800,000 doses of the vaccine,” he told Parliament.

 

The country’s National Health Service would begin vaccination next week, but Simon Stevens, chief executive of NHS England, stressed on Wednesday that the bulk of the vaccination program would take place from January 2021 through to March and April “for the at-risk population.”

[PelicanBill]

I have been concerned that a lot of the good news and timelines are based on what we call in my work an "all success plan"  - nothing can go wrong or unexpected.

 

And today, the Wall Street Journal is reporting this. If true, that means 50% of the current vaccine production failed quality testing. And I would guess it sets back the timeline for healthcare worker vaccination at least 1-2  months.

[Formula280SS]

21 minutes ago, PelicanBill said:

I have been concerned that a lot of the good news and timelines are based on what we call in my work an "all success plan"  - nothing can go wrong or unexpected.

 

And today, the Wall Street Journal is reporting this. If true, that means 50% of the current vaccine production failed quality testing. And I would guess it sets back the timeline for healthcare worker vaccination at least 1-2  months.

 

Yep, read that.  Interesting as it had also been inferred for months that many of the vaccine sources were paid for and were pre-FDA emergency use approved 'manufacturing.  Guess not.  Also, the # of doses for Pfizer has to "halved" for # of recipients with the 2-dose regimen.

 

Pfizer Slashed Its Original Covid-19 Vaccine Rollout Target After Supply-Chain Obstacles

Pharma giant expects to ship half the doses it had originally planned after finding raw materials in early production didn’t meet its standards

[mianmike]

5 hours ago, nomad098 said:

 

Nothing has been subverted but trials have been truncated leaving 3 main questions

 

Will it break transmission?

What is the vaccines long term safety profile?

How long will effectiveness last?

 

If the process had not been truncated we would have probably had these questions answered long  before distribution. 

 

https://www.bbc.co.uk/news/health-55056016

 

 

 

I still don't see where FDA regulatory requirements have been truncated.  But again, I may be missing something.  Hard requirements are different than typical development procedures.  The FDA has sped-up the approval process though. 

 

"The FDA staff have been looking at individual patient data to ask whether its statisticians come to the same conclusions as the companies did. The process is one that "typically would take us months," Dr. Hahn said.  Groups have been working in shifts, nights and weekends, looking in parallel at issues of clinical effectiveness and safety, and of levels of antibodies to confirm the way the vaccine is working."    https://www.morningstar.com/news/dow-jones/2020120212073/fda-head-defends-covid-19-vaccine-approval-process

 

But, IMO you bring up some valid questions.  The main question not answered is: "What is the vaccines long term safety profile?"  That's the risk/reward conundrum.  We know there are documented long-term effects from a covid infection, we don't know if there are long-term side effects from a vaccine.  This vaccine is certainly not 100% risk free.  If it weren't for thousands of people dying everyday and 100s of thousands suffering from the effects and the trashed economy I'd say let's wait and get more data.  It's a calculated risk based on increased knowledge learned from previous pandemic vaccine development re: medical advancements, computer modeling and DNA sequencing.  I'm feeling good our scientists are not putting my health at unnecessary risk.    

 

As for your other questions:

"Will it break transmission?

How long will effectiveness last?"

These questions are valid, will be answered as more data is collected and are something that are important to know, but not critical to the vaccine safety profile such that the vaccine should be delayed.   

   

  

[roger001]

I've said this before, although I can't answer some of those questions about the vaccine, I can absolutely state this.  That without the vaccine, and I then get the virus (my grand daughter was diagnosed positive today but I haven't been around her), anyhow at my age the statistics do show that I have a 14% chance of dying then.   That statistically is a guarantee.  So hmmm.....I'm going to take my chances with the vaccine.   My opinion.  

[nomad098]

24 minutes ago, mianmike said:

 

I still don't see where FDA regulatory requirements have been truncated.  But again, I may be missing something.  Hard requirements are different than typical development procedures.  The FDA has sped-up the approval process though. 

  

As for your other questions:

"Will it break transmission?

How long will effectiveness last?"

These questions are valid, will be answered as more data is collected and are something that are important to know, but not critical to the vaccine safety profile such that the vaccine should be delayed.   

   

  

 

Normal regulatory requirements would require investigations into transmission, longevity effectiveness and long term safety, obviously this is difficult based on limited data from the trials, this would normally have taken months if not years to go over large scale data points from trials.

 

 

 

[mianmike]

11 hours ago, nomad098 said:

 

Normal regulatory requirements would require investigations into transmission, longevity effectiveness and long term safety, obviously this is difficult based on limited data from the trials, this would normally have taken months if not years to go over large scale data points from trials.

 

 

 

Until I hear otherwise I'm going to assume the FDA and CDC are following protocols and are moving the testing into Phase 4 post-approval studies and other post-approval oversight and analysis.  We'll see . . .

[jasperess]

On 12/4/2020 at 10:33 AM, nomad098 said:

 

Nothing has been subverted but trials have been truncated leaving 3 main questions

 

Will it break transmission?

What is the vaccines long term safety profile?

How long will effectiveness last?

 

If the process had not been truncated we would have probably had these questions answered long  before distribution. 

 

https://www.bbc.co.uk/news/health-55056016

 

 

 

The chart on the BBC is misleading as it shows development of a vaccine prior to this time period as well as not in a pandemic era situation with thousands of people dying on a daily basis.

 

Additionally, it is very common in the industry for the FDA to give companies permission to skip Phase II for their drugs if the indication is high priority.  In this case, since COVID is killing a high number of people world-wide so running Phase II concurrently with Phase I and III while still testing it on thousands of patients would be similar to skipping Phase II entirely.

 

Also, there is a lot of discussion on this board about long-term safety of these vaccines.  Of course, long-term safety of these vaccines has not been fully vetted.  However, companies continually gather and process this information in something called Phase IV - not only from people in the clinical trials but also once/if the vaccine gains approval from the independent regulatory board.

[Trimone]

[Formula280SS]

Looks like it's going to be quite a wait for subsequent dosage shipments after 1st one.

 

"Health authorities fear the 800,000 doses of the vaccine could run out just in covering people living in nursing homes and their caregivers—groups already given top priority. And this shipment "could be the only batch we receive for some time," said an official of a National Health Service organization."

 

"The first group to receive the vaccine will be those individuals over the age of 80 living in care homes, as well as their healthcare providers. And even then, demand is expected to outstrip supply"

 

"The initial 800,000 doses promised from Pfizer won’t go far to cover the 3.2 million Brits age 80 and above and the at least 300,000 caregivers working in nursing homes. These people are slated to get the vaccine first, followed by more than 1.4 million NHS workers."

 

"The rest of the population, meaning everyone else under the age of 50, will start receiving vaccinations later in 2021."

Also looks like, after Pfizer announced 50% reduction in production and delivery estimates, and intra-country allocations, and dividing by 2 doses per person, it's going to be a really slow general population vaccination.

 

"The 800,000 doses of vaccine are being shared across the four nations that make up the United Kingdom. Scotland has already said it is receiving 65,000 doses, with Northern Ireland getting 25,000 doses."
 

The most disconcerting note of late is/was Pfizer's CEO comments on their vaccine.  😲

 

https://www.dailymail.co.uk/health/article-9018547/Pfizer-CEO-not-certain-covid-shot-prevents-transmission.html

 

Pfizer CEO admits he is 'not certain' their COVID-19 shot will prevent vaccinated people from spreading the virus - as the firm cuts the number of doses it will ship this year

• Asked in a Dateline interview whether Pfizer's shot prevents transmission, CEO Albert Bourla said the firm is 'not certain about that' 

[GonzoWCS]

Very interesting information here thanks!