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Comment by cf141q5325 | Hacker News Reader

Can anyone explain to me what exactly changed here? As far as i understand it there was nearly zero development effort necessary for COVID. The stuff was basically sitting on a shelf. Yet if i look at older news coverage, it was already clear that once it works, we will basically get a cancer vaccine soon.

edit: The best i can tell its Bayers take on the topic, gene/cell therapy being bad PR. https://youtu.be/OJFKBritLlc?t=5850

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I understand the "cancer vaccine" is actually an enormous simplification. There are certain cancer types that can be triggered by viruses, so a vaccine against these viruses could prevent those particular cancer types. But giving the impression that a general vaccine against cancer is somewhere near seems very misleading.

I'm completely out of my depth when it comes to medical research, but the way I understood the mRNA vaccines against cancer types was a bit more broader than what you suggest: Specific cancer cells produce unique proteins that can be targetted by a "vaccine", so as to enable the body to directly attack the mutated cells. I put vaccine in quotation mark, as it rather seems to be a type of mRNA therapy.

Different approaches just like for prophylactic vaccines, in some cases it's just like an old-school vaccine where dead cells or protein antigen is presented, but yeah cancer vaccines are typically therapeutic rather than prophylactic.

Usually what is meant by 'cancer vaccine' isn't the HPV or Hep.B vaccine where the target is the viral causative agent of cancer. They are typically therapeutic rather than prophylactic, inducing immunity against cancer-specific antigens to overcome the immune evasion mechanisms cancer cells use, tog get the relevant elements of the immune system to attack cancer cells directly. Several are already approved, but no one inn the know is saying that a cure-all cancer vaccine is around the corner, cancers are very diverse and the vaccine approach may only be applicable in very niche cases where cancer antigens are sufficiently different enough from normal proteins expressed by healthy cells — and just like targets of immunotherapy and chemotherapy, there's no promising that cancers won't evolve to overcome therapeutics.

The research was easy, but the development required billions of dollars and literal war-time production efforts (in the US the Defense Production Act was invoked). Drug regulators are also very conservative. Why take risk on making a low-margin mRNA influenza vaccine when other platforms are good enough?

I think a lot of it is that clinical trials are expensive and drug manufacturers generally try to maximize odds of success. COVID was unique because they could get a ton of money to develop and test a vaccine that they knew there would be a ton of demand for if they were early to market with something that worked. now that they've seen how much easier and cheaper mRNA vaccines can be to develop, it's much easier to decide to start a trial.

Full disclosure - I have a long-term (sub $10K) holding of Moderna shares.

The best explanation I've heard for it; is that given by Stephane Bancel (Moderna's CEO) to the (excellent) Bio Eats World podcast in the episode "The Machine That Made the Vaccine" (https://bio-eats-world.simplecast.com/episodes/moderna-covid...)

His explanation goes something like this [0] ...

1) If developers have target protein(s) they know they need to get the body's cells to synthesise to fight disease. Then the key advantage of mRNA technology is that it makes activating this a _turnkey_ operation.

2) With Covid-19, humanity got lucky, the target protein(s) were identified very early in the pandemic, and they have remained useful [1].

These, combined, allowed them to construct a viable vaccine quickly (days) before they had any physical access to the virus. [3]

These new announcements are for diseases where targets are similarly well-identified (and promising from a therapeutic pov). I think the potential for this technology to improve the human condition is, to put it mildly, incredible.

[0] I'm an SW engineer, and it's been over a year since I listened to the podcast, so apologies to anyone if I mangle this.

[1] For some diseases, this is apparently not the case, e.g. AIDS

[3] Of course it then needed the same standard, thorough acceptance process, albeit accelerated by running parts in parallel, before being released to the general public.

Once you get the genetic sequence sequence you want, you can "print" out the vaccine. After BioNTech received the genetic sequence of SARS-CoV-2 in email, they had small batch vaccine candidates out ready for animal testing within days.

There are still other steps that take time. You need to figure out what is the mRNA you want, then you need to test a new vaccine candidates for adverse effects.

It would have taken many years to get the new technology approved, but we skipped a lot of that due to the pandemic. Now that we have lots of safety data it is easier for them to get new vaccines approved.

Most of the years skipped though was red tape, bureaucratic slog, fundraising, clinical trial participant recruiting, and having a high enough absolute risk of infection in the population that it was not long at all to have a significant difference in effect between treatment arms.

It probably helps that there's now a well develiped framework for mRNA and adenovirus vector vaccine approval, but ultimately any new antigen could certainly be unsafe and future candidates are going to require every bit as much testing and won't get most of the expeditiory benefits the first generation of COVID vaccines experienced.

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