Member Info for RayPointer

Hi Bermuda

I appreciate that these organisations exist and I applaud their aims and aspirations. But when it comes to the crunch will such organisations provide the solutions we need? Will they attract the best brains in the industry and academia?
Will governments support these organisation over and above their own companies and universities?
It's not a case of working hard to make the breakthroughs, it's a case of having the best talent working hard in teams.

Having said all that, sometimes it just takes 1 individual to make the crucial breakthrough. The history of science shows us that.

What gets me over the search for an effective Covid19 vaccine is that there appears to be no tangible co-operation between countries and/or companies on a global scale.
There is nothing of the "project blueprint" spirit of joining together some of the best brains in acedemia and companies.
So universities are going their own way to create a vaccine as are individual companies. Governments are also letting this happen.
The result is that huge amounts of money are being spent on what in many cases will turn out to be mediocre solutions to the problem.
I'm not saying this should be stopped and we should be concentrating on only one solution, merely that governments should encourage a more collective approach to solving the problem utilising the planet's best scientists.

History has been made

IMO, it is not just about targeting both S and N proteins but it is about choosing the best epitopes to target within those proteins.
You don't want the same epitope to exist on proteins expressed by healthy cells.
Of course, the high avidity that immunobody creates is also very important.

"Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19."

Note the word "therapeutic".

Also, it may be that targeting to N protein will future proof the vaccine against future mutations to a limited extent.

Thanks Inan

I will have a read

Thanks Inan

"nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine"

I assume these are PTMs in addition to the main Modi1 PTM "arginine to citrulline".
I can't recall these being talked about by Lindy.

Sounds like she was working on something at the time.

https://www.cancerresearchuk.org/sites/default/files/portfolio_lists_for_website_may2020.pdf

I think this has been posted recently but I see we are still at "exploratory" for SCIB2.

I noticed that vaccitech (spinoff from Oxford Uni) are also planning a trial in NSCLC with their vaccine VTP-600.

More about this here
https://www.vaccitech.co.uk/pipeline/

I wonder if anyone knows more about this vaccine that appears to be based on ChAdOx1 which I believe is the same platform as Oxford's Covid19 vaccine.

NSCLC patients will receive VTP-600 in combination with chemotherapy and anti-PD-1 standard of care.

Thanks for the clarification Bermuda.
The wording makes it misleading IMO.

So this may be "a person closely associated with Martin Diggle" who has invested in Vulpes, as it was last time.
If this is the case, then we should get an RNS tomorrow.

This in no way indicates that SN11 is bound to be successful.
It is just that Lindy and her team are skilled at finding targets and with Immunobody the resultant activated TCells are both high in avidity and numbers produced.
Only some of these TCells will become memory TCells, but it is thought that these memory TCells are long living and quickly become effector TCells when the virus puts in an appearance.
I don't know whether Lindy is thinking in terms of a preventative vaccine only or whether she possibly thinks that SN11 may also be a therapeutic vaccine.

We need to bug Lindy's Nottingham lab.

I'm saying that possibly Lindy's approach may be more effective if Covid19 evolves in the same way that another coronavirus (the common cold) evolves.

SN11 targets both S and N proteins.

But Lindy may even find epitopes on the S proteins that also remain constant as the virus mutates.
But, so far, she has not indicated that.

Remember an Immunobody vaccine can have many targets (SCIB2 has 16 and they are all on the same protein i.e. NY-ESO-1).

https://www.technologynetworks.com/immunology/news/why-dont-we-ever-develop-immunity-against-the-common-cold-294551

This is an interesting little article that pre-dates the pandemic.
In the case of the common cold, it seems that the Spike (S) proteins evolve to evade the antibodies produced on a previous infections of the common cold.
It could be that it is absolutely essential to find epitopes that remain constant as the coronavirus evolves and produces new strains including these different variants of the S proteins.

Interesting WTP

I wonder if the relevant TCells are the type that attack the N protein that Lindy says is probably a constant in all Coronaviruses.

Sounds like the Oxford and Imperial vaccines were peer-reviewed by Dominic Cummings.

Some bedtime reading

https://www.frontiersin.org/articles/10.3389/fimmu.2019.01529/full#:~:text=Dendritic%20cells%20(DCs)%20facilitate%20cross,innate%20and%20adaptive%20immune%20system.&text=Polarized%20T%20cells%20in%20turn,of%20the%20resulting%20humoral%20immunity.

"Concluding Remarks
Delivering antigens to cDCs has garnered much attention as a method for enhancing CD8+ T cell responses. We strongly believe that the potential to influence CD4+ T cell polarization, and consequently antibody class switching, are of equal importance. Especially when considering the observations that IgG-subclass and Fc-mediated effector functions strongly influence the protective ability for broadly neutralizing antibodies against influenza and HIV. When also considering the ability to actively manipulate the magnitude and quality of the antibody responses, DC targeting will be a valuable tool for further vaccine development."

Immunobody targets epitopes regardless of whether they are self or non-self.
The point Prof Patel was making was that for Immunobody to target a non-self epitope (an invader as he put it) should be easier than targeting an epitope that the immune system regards as self (i.e cancer) . The non-self epitope is less likely to be defended by TRegs.

So the question should be :
Is mounting a TCell attack on a virus a viable option to clear the virus?
There seems to be evidence that the answer is yes for Covid19.

So the process is the same
a) find the targets
b) ensure it is safe to attack these targets (they don't exist on healthy cells)
c) check that naive TCells exist in humans
d) test on animals
etc.

Lindy is targeting epitopes on the S protein as well as the N protein and in addition producing neutralising antibodies.
There is no doubt extra work required to create the neutralising antibodies but she has Prof Ball and his crew as well as Nottingham Trent staff to help with that.
I recall Prof Ball saying he had designed some of the inserts to the vaccine, presumably these are used by the Dendritic cells to promote the production of the neutralising antibodies.

Hi Ruck
I actually believe it is more like what Ivy says about big pharma being obsessed with their own chosen route to success.
They invest huge sums on that route and this in turn benefits companies like Biontech who provide the research whatever the route.
So, to me, the prime example of peer acceptance is the membership of Ira Mellman and Ugur Sahin on project blueprint. These 2 gentlemen must have seen numerous attempts at defeating cancer using different methods. Both have been in the game of a long time and have great respect from their own peers. They understand the potential of Moditope and hence decided to join the team. To me that speaks volumes especially for Ugur who is CEO of a highly successful research company himself.

So, it appears, that the obsession of boards to follow a chosen path has not spread to scientists (at least in respect of these 2 gentlemen).

To me the most important aspect of Scancell is that quality science keeps on coming.
The quality of science I judge mainly by the attention it attracts from other well respected scientists.

Who's not to say that Covidity/SN11 is not the latest example of that quality science? Lindy has perceived that what is missing from most Covid19 vaccines is a strong TCell response and maybe it is essential. Time will tell if she is correct but there is growing evidence that she is.

Crumbs did some research on up front payments for mABs and, as I recall, the going rate was on average 10 million dollars per mAB.
I'm not saying we will get that, Scancell may have a buy 1 get 1 free promotion.
There is also the fact that 1 collaborator is looking at Avidimab as an adjuvant i.e applying it to existing mABs.

So against getting a good price is that Scancell really need the cash. They may consider cash for Avidimab to be an added bonus to some extent.
The argument for getting a good price is that there are 3 collaborations. What if 2 or 3 like what they see?