Risks of Cuts to mRNA Vaccine Development | Johns Hopkins

For some background, can you tell us a little bit about standard vaccine types and how they work?

Vaccines train our immune system to recognize and respond very quickly to a bacteria, a virus, or even a protozoa, like the one that causes malaria. Then, if we’re actually infected with that pathogen, our immune system can respond much more quickly to minimize our risk of disease.

We have a long history of vaccines, going back two centuries to when vaccines were first developed for smallpox. First, we have attenuated vaccines, which use a weakened form of a virus—like measles, mumps, or rubella viruses—to introduce the virus to our body. They don’t cause disease, but they can train our immune system to respond.

Inactivated vaccines, like the inactivated polio vaccine and the rabies vaccine, use a killed bacterium or a virus that can’t replicate anymore. That inactivated pathogen is introduced into our body to train our immune system.

Another older vaccine is called the toxoid vaccine, which is used to treat bacteria that produce toxins, such as diphtheria or tetanus toxins. We inactivate that toxin, which is a protein, and inject it into the body to train our immune system.

Subunit vaccines, which are a recent development in the past several decades, use a key part of the pathogen rather than a weakened or killed version and use that to train our immune system. Examples include the hepatitis B vaccine, as well as some vaccines used against pneumococcus or Haemophilus influenzae, which are pathogens that can cause pneumonia or meningitis.

How does the mRNA vaccine work?

The mRNA vaccine uses a different strategy, and it’s a very clever strategy. Instead of using part of a virus or a whole virus like in other vaccines, mRNA vaccines use part of a virus’s genetic code—the RNA—that encodes for a significant protein on the virus’s surface. When that is administered into our body and is taken up by our cells, it allows our own body to produce the protein [and mount an immune response to it]. 

In COVID vaccines, the virus is SARS-CoV-2 and the main protein we’re interested in is called the “spike” protein on the surface of that virus. We insert the mRNA for the spike protein, and our body is then able to make that spike protein for a limited amount of time, which is then excreted from the cells. It’s another way of training the immune system by having the body actually produce the protein rather than introducing the protein itself. 

Why are mRNA vaccines considered a groundbreaking technology?

What makes this technology so exciting and so important, and why this pullback of the funding for mRNA vaccine development is so tragic, is that the mRNA vaccines can be developed and adapted very quickly. For COVID, we had the genetic sequence of that virus within a week or two of identifying the outbreak, which was all that was needed to make an mRNA vaccine.

If we have a pathogen like SARS-CoV-2 or influenza that mutates, or a new pathogen like bird flu, we can change the vaccine very quickly to keep up with the evolving virus. It makes this vaccine technology important for treating emerging pathogens, particularly those evolving quickly.

Are mRNA vaccines safe and effective?

These vaccines are safe and effective. In withdrawing this funding for mRNA vaccines, Secretary Kennedy made the false statement that these vaccines are not effective against respiratory viruses. They’re very effective against respiratory viruses. We saw that during the COVID pandemic, where the COVID mRNA vaccines prevented millions of deaths.

When we talk about vaccine effectiveness, it’s important to talk about the outcome. These vaccines, and vaccines in general, don’t prevent us from getting infection. What they’re really designed for is to prevent disease, particularly severe disease, hospitalization, and death. mRNA vaccines for COVID do this very well.

No vaccine or drug is perfectly safe. There are adverse events associated with mRNA vaccines, many of which are very rare and very difficult—if not impossible—to detect in clinical trials. When suspected adverse effects turn up, we have very sensitive systems to identify them and pursue further investigation and further studies.

For example, myocarditis, or inflammation of the heart, can follow a COVID mRNA vaccination, particularly in young men. It’s quite rare, maybe 20 or 30 cases per million doses. However, we know that the risk of myocarditis is close to 10 times higher with natural COVID than following the vaccine. So there’s still a risk benefit ratio in favor of vaccination, even in higher risk populations.

What do you think is behind this decision to cancel funding?

There has been a lot of misinformation about mRNA vaccines, falling into two buckets. One is the belief that these vaccines are not effective against respiratory pathogens, which is patently false. Second is the belief that these vaccines are harmful, which is also false.

Some people believe that these vaccines were developed too quickly. But there had been at least two decades’ worth of work on these types of vaccines before the COVID pandemic, and we were just poised to put them into practice during the pandemic. And they saved millions of lives.

Unfortunately, we saw a very tragic shooting at the CDC last week that was, in part, fueled by disinformation around COVID vaccines. Allegedly, the shooter believed that he had been harmed by an mRNA COVID vaccine. 

Do mRNA vaccines alter your DNA?

No, mRNA does not alter DNA. All of our cells are full of mRNA molecules; it’s how we make proteins. There’s nothing unnatural about mRNA. What these vaccines are doing is just giving our cells a different menu or set of instructions to make a different protein, which will then train our immune system. 

What mRNA vaccines were we expecting to see that these cuts will affect?

$500 million was cut from 22 grants that were awarded by the Biomedical Advanced Research and Development Authority, or BARDA, which largely works on tools and vaccines for emerging infections and pandemics. The biggest impact is going to be on our preparedness and national security for the next emerging pathogen or pandemic.

But mRNA vaccines have huge potential beyond emerging pathogens. There’s a lot of exciting early research around mRNA vaccines for other infectious diseases like HIV, where we haven’t had success with other types of vaccines. There’s also a lot of excitement about using these mRNA vaccines to treat cancer, like pancreatic cancer, or for autoimmune diseases like type 1 diabetes or multiple sclerosis.

This undermining of public confidence in and federal funding for mRNA research is really going to set us back. Other countries will move forward and we will be stalled.

Does this cancellation of mRNA research make us less prepared in the future?

This does make us less safe going forward. We will not have the advances and the readiness to respond to another new pathogen or another pandemic outbreak, which will inevitably happen. We know that we’re going to see new emerging pathogens, maybe even new coronaviruses.

It would be tremendously ironic if, in the second Trump administration, we undermine what happened during the first Trump administration. It was under Donald Trump that Operation Warp Speed was funded and mRNA vaccines against COVID were rapidly put into clinical trials.