Why are mRNA vaccines not yet available against other diseases?

Question

The mRNA vaccines against developing COVID-19 are obviously the first approved mRNA vaccines. We are probably at the beginning of an mRNA vaccine evolution. I've recently read a very interesting article about the development of a potential Herpes Simplex (HSV-2) vaccine. https://www.precisionvaccinations.com/can-mrna-vaccines-defeat-herpes:

The goals of a HSV-2 vaccine are to keep the herpes virus dormant. Or if the virus escapes, prevent it from causing symptoms. ... This superior molecular response was consistent with symptom reduction - the mRNA vaccine was perfect in preventing genital disease (100%) and significantly reduced recurrent disease (98%). ... The risk of transmission (measured by days) was 2% with the protein vaccine, compared to 0% with the mRNA vaccine.

And a new mRNA vaccine against seasonal influenza (mRNA-1010, mRNA-1020, mRNA-1030), a HIV vaccine (mRNA-1644 & mRNA-1574) and the Nipah virus (NiV) vaccine (mRNA-1215) and others such as vaccines against Zika virus, Epstein-Barr virus (EBV), CMV, RSV and hMPV. This all seems very promising. - https://investors.modernatx.com/news-releases/news-release-details/moderna-provides-business-update-and-announces-three-new. As well as a Malaria vaccine.

But my main question is, what is there to develop? Isn't the over simplified process of mRNA vaccine production not something like: identify, sequence, isolate, find a proper carrier, produce? I can imagine that once the general production of mRNA vaccines is available and approved that it is just matter of putting other genetic material in the vaccine carrier?

Answer 1

A few-year-old review that might be useful is:

Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17, 261–279 (2018). https://doi.org/10.1038/nrd.2017.243

The tricky part of creating an mRNA vaccine once the "platform" has been developed remains exactly what mRNA sequence do you put into it? Remember, the virus sequence is selected for infection and replication; the sequence for the vaccine should NOT do that, but still should generate an immune response that will stop the actual virus (perhaps antibodies, perhaps cellular, perhaps both). And of course, you don't want something that accidentally causes a bad side effect like a misdirected immune response.

For Covid, it turns out a key factor in creating successful vaccines has been pre-existing work to modify the spike protein so it holds a certain shape that normally is only transient: see https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38

In any case, you've still got to test your candidate to make sure it generates an effective immune response and doesn't have any major side effects.

Answer 2

From the links you've supplied, none of these other vaccines have gotten further than phase 2 trials yet. Most seem to only have phase 1 trials started or merely planned so far.

These vaccines are not yet available because they have not completed clinical trials that demonstrate safety and efficacy.

Answer 3

I know at least one far more deadly rare disease 1 for which an mRNA vaccine has been developed and shown to work in the lab. The treatment is likely to work for MOG antibody disease. Maybe the lack of a business model is a major factor in why phase 1 trials for this mRNA vaccine 2 for that disease were not even being discussed at all in this ~40 -minute YouTube presentation on it by two of the researchers who invented and tested it/demonstrated efficacy in several ways in the lab.

Maybe a trial is being discussed and will happen. But it is common for approval for and further testing of drugs which appear to be quite effective to not be pursued because of the lack of a business model.

The US and EU orphan drug strategies are an attempt to address this problem. (In my view, this created a two-tier system that is better than a one-tier system, but retains all the problems that caused the one-tier system to be modified. They're just a bit smaller, on average.)

Also, and this is particularly relevant to the OP's question, there were (appropriate) shortcuts taken in development of the CoViD-19 vaccines. A lot of unnecessary work was eliminated, investment and decision making were sped up, manufacturing investments were made prior to the existence of clinical trial evidence. (6 ibid. ~ t=1200s) Re-reviewing the video, I note that Ugur Sahin suggests that perhaps some of these shortcuts are also appropriate specifically in situations of high medical need and standard development timeline of > 10-years - like the one I document here. (5 ibid. ~ t=1340s)

Compared to the way the disease is currently treated (broad suppression with prednisone long term, acutely with megadoses of prednisolone, indefinitely with rituximab, azathioprine, etc.) pinpoint immune system tolerization to self is likely to be much, much safer.

Inventors of what's best known as the Pfizer mRNA vaccine and the MOG m1[PSI] mRNA vaccines -the esteemed scientists who have created these vaccines are not wrong to call them both "vaccines". They have worked tirelessly in this research area for many years. Tolerizing mRNA vaccines are about as traditional as any other mRNA vaccines. They are hardly a new concept as they have been in development for many many years; certainly 7; probably ~3x more. Its analogous that we still use the term atom, even though the definition has changed radically over the centuries.

There is more than one kind of EAE. Murine EAE is always caused by improper immune response against the self, but here it is specifically caused by an anti-MOG antibody induced by "immunizing" the mice, causing paralyssis. (14:40 in the presentation.) And the treatment used is MOG m1[PSI] mRNA.

Again, notably, the people who created the MOG m1[PSI] mRNA vaccine and do call it a vaccine are largely the SAME experts that invented the particular famous "mass-market same-for-all immune-stimulatory" disease preventative injected into billions of arms manufactured by Pfizer.