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Burble,
Many thanks for your valued input, along with a few others that contribute to my understanding of the science of this great little Bio.
IMO it is down to the science and IP that makes this such a good investment along with, so far, no negatives on that front.
Could it fail, yes of course, but nothing yet to indicate otherwise.
I would just like to add that for the last 8+ years of being in this share a large majority of understanding the science has come from Inanaco and a small number of other valued posters. You, now coming on stream just adds to that, fantastic for me.
I will say however that there are a number of posters on this BB that have an agenda simply because they have developed a certain complex about Inanaco's STYLE of posting, if they could allow their ego's to get over it then this BB would be a better place altogether.
Chester seems to have a good slant on things here IMO.
ATB
Bunsie (filtered by??)
Yeah allotment is currently my only escape from life. Normally I’d be elsewhere but team sports aren’t allowed at the moment.
Thanks Burble. I will take me a bit of time to get my head around everything you said but it does appear that amplivant is multi-functional. No problem in the time taken to answer. It's just great to have someone of your knowledge posting.
Thanks Burble for explaining it all in such a clear fashion.
My knowledge of adjuvants especially Aluminium based ones is all to do with Viral Vax and is simply there to improve the efficacy especially when it is killed or attenuated antigen etc.
Seems the adjuvant has a much wider role in cancer Vax which you have highlighted.
Hope you enjoyed digging in the allotment.
Spent many happy hours in a Northumberland Allotment many moons ago.
Addendum 3/2/end
Something I hadn’t really also thought through. Moditope relies solely on CD4+ cells. Immunobody on CD4+ and CD8+. Thinking aloud here, as they work through two different mechanisms and would be on two different targets….there may be an opportunity to try them both together.
Imagine this scenario – SCIBx targets molecule Y.
Cancer initially responds to SCIBx as it has molecule Y on it’s surface. If SCIBx doesn’t clear this entirely and the cancer mutates or loses this target on it’s surface, moditope is given to clear up the rest.
or
Cancer responds to Moditope with the booster function of SCIBx as it has molecule Y on it’s surface. If the molecule Y mutates and so SCIBx loses function, there is no need to wait for the cancer to grow and show on scans because moditope has already been given and is working away in the background.
Also think of these in a different light. A lot of people survive their initial cancer, but die of the secondary metastises that may have already seeded themselves around the body. SCIBx would already be searching those out (if they have the target molecule on the surface), moditope may not be needed until the cancer starts really growing and showing the resulting cellular stress-induced post translational modifications. Hence clears up afterwards.
Firstly, (and this is an assumption I am making) Amplivant probably helps extend the time Moditope petides are in the blood stream/site of vaccination. Secondly, Amplivant (and it’s payload) binds TLR1/2 receptors on the surface of the cell. In doing so, it triggers the TLR signalling cascade which results in pro-inflammatory cytokine release and dendritic cell activation. In turn, this results in inflammation and in doing so an up-regulation of MHC-class II molecules on the surface of the dendritic cell. At the same time, other moditope peptides in close proximity to the surface of the dendritic cell and so are engulphed by the cell membrane through a process called phagocytosis (literally Greek for to eat and cell). The moditope peptide is then broken down and loaded onto the MHC Class II molecule. This then is trafficked to the surface to present the peptide to a helper T-cell. Third and forth) In turn, the helper T-cell release other cytokines which recruit other cells to help combat this target.
So Amplivant does the following
- physically takes Moditope peptides to the APC
- activates signalling pathways which upregulate MHC Class II proteins
- Increased MHC Class II proteins means more opportunity to APC to present moditope peptides to CD4+ helper T-cells.
- Increased inflammation meaning recruitment of further immune cells, which potentiates these steps. In turn helping reduce the amount of peptide needed to obtain a result.
The reduction in the amount of peptide needed translates two fold – firstly into how much of a dose you have to give somebody to see an effect (good for the patient), reduced costs to manufacture (increasing profit margins and potential market size).
2/2
RP,
I didn't mean to ignore your question. The last few days have been a bit of a rollercoaster for me, so haven't really had a chance to put something down on paper. So in response to your statement 'I hadn't realised that amplivant helps the vaccine find its way to the DC.'
The immune system – specifically the innate immune system is able to recognises specific structures present on bacteria or viruses known as pathogen-associated molecular patterns. These for example can be viral or bacterial components such as proteins, carbohydrates, fats (lipids) or nucleic acids (DNA/RNA). These PAMPs are recognised by a range of different receptors, one of which includes the Toll-like receptor family. The TLR family of proteins are found on the surface or inside many immune cells such as antigen presenting cells or dendritic cells to name a few.
When a TLR ligand binds to it’s target binding partner, a signalling cascade is initiated within the cell (https://bit.ly/2FZZkt9) which results in the activation of this cell. It also results in the secretion of pro-inflammatory molecules such as cytokines and upregulation of other co-stimulatory molecules.
Binding of a TLR ligand, results in activation of the adaptive immune response as dendritic cells migrate from the site of infection to the nearest lymph node where they present bacterial/virally derived antigens to naïve CD4+ cells. At the same time dendritic cells express co-stimulatory molecules which result in the differentiation of CD4+ cells into TH1 cells or TH2 cells.
So where does Amplivant come in?
Amplivant is an adjuvant, which is a chemical or immunological substance that is added to a vaccine to improve the immune response. An adjuvant is designed to stimulate the immune response but also to help modify the immune response to bias it towards possibly an antibody response or alternatively to a T-cell response. Common adjuvants include things such as aluminium hydroxide or paraffin oil. Adjuvants work by a range of mechanisms including a) extended the time that an antigen is present in the blood (and therefore being presented to the immune cells), b) helping the antigen presenting cells absorb the antigen, c) activating other immune cells such as macrophages and lymphocytes or d) helps support the production of cytokines. I would say most likely in this case it is all of these.
From what we know Amplivant is a modified Pam3CSK4 (https://bit.ly/3j1rN0k) - which in itself is a synthetic triacylated lipopeptide that acts as a TLR1/2 ligand (for clarity, lipopeptides are a peptide with a fatty molecule on the end) which can itself be joined onto synthetic long peptides (i.e. moditope peptides).
1/2