Moderna's mRNA Vaccine Approach

[gardening-girl]

This is the best diagram I've seen so far depicting the way Moderna's mRNA 1273 vaccine is expected to work.* It highlights the fact that the introduced mRNA (spike protein mRNA1273 in the case of the SARS-CoV2 vaccine), enters myocytes in muscle tissue as well as macrophages, dendritic and B cells, in lymph tissue, where it is translated through the process of protein synthesis, producing the SARS-CoV2 spike protein antigen, which is subsequently either secreted from the cells, or processed and presented at the cell surface,

1. available for binding to the BCR (B cell receptor) of a nascent B cell leading to its conversion to an anti-spike protein antibody producing plasma cell, and perhaps a memory cell B cell as well,

2. or binding to a T cell receptor leading to activation of the T cell.

Reading Neil's recent post about the importance of T cells in fighting COVID-19 led me to post this diagram showing how Moderna's vaccine is not only expected to lead ultimately to the synthesis by B-cells of anti-spike protein antibodies, but that it also is expected to activate T-cells as shown in the diagram.

modernatx.com/moderna-blog/...

* The cartoon was made in 2017 when Moderna was studying other mRNA vaccines.

Thanks Neil for the nudge I needed to present the Moderna approach diagram which I just discovered this evening.

gardening-girl

Some other reading of possible interest:

1. Links to 2017 papers from Moderna explaining their vaccine strategy which includes modifying ribonucleotide bases in the RNA to make it more stable, and encapsulating the RNA into a specially designed lipid nanoparticle:

cell.com/molecular-therapy-...

sciencedirect.com/science/a...

2. The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race

statnews.com/2020/11/10/the...

3. Why does Pfizer's COVID-19 vaccine need to be kept at a lower temperature than Moderna's:

npr.org/sections/health-sho...

[Jm954 Administrator]

So much great information there, really well illustrated too. Many thanks for posting. :)Jackie

[Smith123456]

but is it's unique approach safe for someone with cll?

[GMa27 in reply to Smith123456]

Exactly

[gardening-girl in reply to Smith123456]

Smith123456, et al.

The Moderna and Pfizer vaccine candidates are not live or attenuated viruses, so I don't know of any reason why they would not be safe for us. Nor can they replicate or mimic the virus within a cell.

However, unfortunately, because their effectiveness depends on eliciting an a robust immune response, as do all vaccines to date, they may not be effective for those of us who are immunocompromised!

Just as IgG infusions (IVIG) protect us from many pathogens, infusion of a synthetic anti-SARS-CoV2 spike protein antibody would have a much better chance of providing protection. Synthetic anti-SARS-CoV2 spike protein antibodies are being developed, and some are in clinical trial, but for therapy, not prophylaxis.

I've provided links to three groups who are working on synthetic antibodies. Perhaps just as anti-CD20 antibodies (rituximab et al.) are available for CLL treatment, someday if the pandemic persists, maybe these synthetic anti-SARS-CoV2 spike protein antibodies will be made available for prophylaxis under certain circumstances, or better yet, if there are enough anti-spike antibodies circulating in the general population they will show up in the IVIG to which we now have access! Wouldn't that be wonderful!

"By screening hundreds of synthetic antibodies, researchers at Karolinska Institutet in Sweden and EMBL Hamburg in Germany have identified an antibody that may prevent the new coronavirus from infecting human cells."

news-medical.net/news/20201...

"A company developing synthetic genetic materials and proteins says independent tests show its artificial antibodies neutralize infection mechanisms in Covid-19 viruses. Twist Bioscience Corp. in South San Francisco, California says tests of its synthetic antibodies were carried out and verified separately by labs at two different universities."

sciencebusiness.technewslit...

'The biotech Regeneron Pharmaceuticals has developed a cocktail of two monoclonal antibodies that attach to the surface protein of that coronavirus, SARS-CoV-2, and attempt to block it from infecting cells. Yesterday at an investor and media webcast, the firm revealed early results.''

sciencemag.org/news/2020/09...

gardening-girl

[bennevisplace in reply to gardening-girl]

In addition, Astrazeneca is going into phase 3 trials on AZD7442. I posted about it this morning. The drug is not exactly a synthetic, I believe, but derived from convalescent plasma. It is specifically aimed at clinically vulnerable people who may not respond to Covid vaccines.

AZD7442 is a combination of two LAABs derived from convalescent patients after SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the LAABs were optimised by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extended LAABs should afford six to 12 months of protection from COVID-19.2-5 The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.6

In a recent Nature publication, the LAABs were shown in pre-clinical experiments to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.

[gardening-girl in reply to bennevisplace]

You did get me started reading about this! The two monoclonals were definitely based on cells isolated from convalescent plasma, but are indeed synthetic cloned proteins produced in CHO cells.

[bennevisplace in reply to gardening-girl]

Thanks for clarifying that.

[GMa27]

All that is way above my understanding. I just want to know if it's safe for me or anyone out there to have. My hematologist said not to get it when it comes out and wait. It was developed way too fast. I see her again in May and hopefully know more by then.

Problem is a lot of people don't believe in vaccines anyway and many won't even get it. Covid will be a threat for a long time. 😟

[Smith123456 in reply to GMa27]

i asked the question because it's unique approach 'might' mimic a live vaccine. As you know we can only use 'dead' vaccines. I will take a 'dead' vaccine.

[GMa27 in reply to Smith123456]

Yes we can only take dead virus. But I will wait till next Spring/Summer to decide.

[JigFettler Volunteer]

Even that presents challenges, though — a Pfizer scientist told a CDC advisory council in August that it's not supposed to be opened more than twice a day and needs to be closed within one minute of opening. Once it's thawed, the vaccine can be refrigerated for five days.

Moderna says its vaccine candidate is stable at regular freezer temperature — minus 20 degrees Celsius — for up to six months, and after thawing it can last in the refrigerator for 30 days. It can also be kept at room temperature for up to 12 hours. This, explains Kristensen, is useful for health care workers in the field, "because now the vaccine doesn't need to go in and out of the refrigerator each time it's administered."

Very interesting and helpful. Good links. The above interested me - I was imagining how a vaccine at -70degC was going to enter my body! Now I know!

Jig

[bennevisplace]

Thanks, that's another stack of weekend reading!

I've also got two pianos to move , an office to clear out, a rugby international to watch...

[mrsjsmith in reply to bennevisplace]

Don’t forget the tennis as well.

Colette

[AussieNeil Partner Administrator]

More on the mRNA vaccination approach:-

Want to Know More About mRNA Before Your COVID Jab?

— A primer on the history, scope, and safety of mRNA vaccines and therapeutics

medpagetoday.com/infectious...

The article notes: Never Been Done Before? That's not completely true. While an mRNA vaccine has never been on the market anywhere in the world, mRNA vaccines have been tested in humans before, for at least four infectious diseases: rabies, influenza, cytomegalovirus, and Zika.

Neil

[AussieNeil Partner Administrator]

mRNA Mythbuster, following the Therapeutic Goods Administration (TGA) provision approval of Australia’s first COVID vaccine, the mRNA based Pfizer vaccine:

Myth 1: they enter your DNA and change your genome

Myth 2: they connect you to the internet

Myth 3: they cause autoimmune disease

Myth 4: they make you infertile

theconversation.com/not-sur...

All busted.

Neil