mRNA vaccines could change everything in the fight against disease

Despite the rumblings of the anti-vaccination movement, vaccines are a crucial and effective weapon in the war on infectious disease. Armed with vaccines, polio and measles were brought to heel, and smallpox, among the most catastrophic diseases in human history, was wiped from the face of the earth, save two freezers.

Faster, cheaper, and safer, RNA vaccines show great potential to meet evolving threats.

But important as they are, vaccines have weaknesses. Against the new emerging viruses — dreaded pathogens like Ebola, Marburg, and Zika — and the difficult-to-pin-down influenza, traditional methods of vaccination have come up against difficult challenges. They can also be expensive and time-consuming to produce, curtailing efforts to control outbreaks or head off a flu season caused by an unexpected strain.

A newer type of vaccines, using RNA, could alleviate these issues. Faster, cheaper, and safer, RNA vaccines show great potential to meet evolving threats.

How do Vaccines Work?

How vaccines work is fairly simple. When the immune system is exposed to a disease-causing agent — a pathogen — it creates antibodies. These large, y-shaped proteins jam themselves onto the attacking pathogens, disabling them or marking them for death by the various defenses of the immune system, like the cell-devouring macrophage. Once the antibodies have been created, the immune system will recognize the pathogen if it infects the body again.

The dangerous nature of these viruses requires specially equipped labs to study them.

Vaccines work by causing the immune system to create antibodies before it comes into contact with the real pathogen. This makes vaccination unique in that it is preventative in nature: it effectively stops the disease before it even begins by setting the alarm. Vaccines achieve this by using antigens — the protein signature of a pathogen, which triggers the immune response — to kickstart antibody creation.

This works pretty well if scientists know what they’re guarding against. But emerging diseases may never have been seen before by science, so a basic lack of knowledge hamstrings new vaccine production. The dangerous nature of these viruses requires specially equipped labs to study them, which creates a bottleneck in gathering that knowledge.

After the basic research is done, producing a vaccine’s unique antigens and ingredients at scale requires a huge investment in a specialized facility, which usually takes years to build. The challenges in working with the viruses make growing a large culture of them difficult, and the financial rewards are often minimal at best.

Even well-known viruses can give vaccination fits. Influenza is the Loki of the virus world, able to take many different forms by mixing up the proteins on its outer coat, mutating so rapidly that the antibodies from last year’s flu may not recognize the threat.

Before the flu season begins, health officials have to make an educated guess about which types of flu will be most common and produce a vaccine for those strains. If they choose wrong, or you encounter a slightly different type of flu, the vaccine antibodies won’t be as effective. (This is why anti-vaccine movement propaganda on Facebook says the flu shot is “useless.”) Often, by the time we know for sure, it’s too late to make or distribute a new vaccine.

Health officials have to make an educated guess about which types of flu will be most common and produce a vaccine for those strains.

RNA Enters the Fray

Fortunately, there are multiple types of vaccines in development. RNA vaccines use a different method to goose antibody production, but to explain it, we’ll need to brush up on our high school biology (this’ll be quick, promise).

In short: DNA is the genetic blueprint of a cell. To go from the blueprint to construction, the cell uses messenger RNA (mRNA), which is essentially a set of directions, written in genetic code, that tells the cell how to create different proteins.

In a traditional vaccine, the antigens are made in a lab, using inert viruses or their parts and proteins, and then packaged up and distributed to doctors, where you get them in a shot.

Unlike other types of vaccines, RNA vaccines contain mRNA instructions to make the antigens inside the body. The vaccine instructs cells to create the antigen, which in turn gets the immune system to cranking out antibodies. Immunity then follows, just like with a conventional vaccine, and the body is ready to recognize and fight off the real attacker.

This has numerous potential advantages.

The RNA vaccine instructs cells to create the antigen, which in turn gets the immune system cranking out antibodies.

Because mRNA instructions are all written in the same simple genetic code, it can spell out the instructions for making almost any kind of protein antigen, for almost any disease; only the genetic code of the candidate is required. That means RNA vaccines can be mass produced cheaply, quickly, and by standardized methods, which can be easily ramped up in case of a new disease or a surprise flu strain.

That means that a single facility could make different types of vaccines against many different diseases — hugely reducing costs. They also don’t require a stock of pathogens be grown and stored in order to make the antigen ingredients (a time-consuming and expensive process).

RNA vaccines may be safer than other techniques, too. Since they do not contain any elements of the pathogen itself, there is no risk, no matter how minute, of causing infection themselves (a fear leveraged to fuel manufactured, scientifically unsound vaccine controversy) and, unlike DNA vaccines — a similar approach that uses DNA instead — messenger RNA cannot impact the basic genetic code of a cell.

While more testing is needed, results so far suggest that RNA vaccines are effective in providing immunization and have few side effects. The same technique also shows promise in developing vaccines for cancer treatment.

The Cold Water

RNA vaccines do have their drawbacks. Chief among them is the vaccine’s need to be kept cold.

Despite their potential, RNA vaccines do have their drawbacks. Chief among them is the vaccine’s need to be kept cold, an issue with other types of vaccines as well. Having to be refrigerated makes it difficult for vaccines to be deployed where they may be most needed, like in remote areas or the middle of hot zones. This issue does not seem to be insurmountable, though. CureVac, a leading German manufacturer of RNA vaccines, is currently working on solutions that eliminate the need for cold storage.

The delivery method inside the body is another tricky aspect: RNA just floating around is quickly destroyed. To ensure the RNA arrives at the cell, it needs to be packaged into another, larger molecule. Some RNA vaccines use longer strings of mRNA to program the cell to create the antigens multiple times, meaning more immunity from less vaccine. But because they are longer strings of code, they are even more susceptible to degeneration.

Perhaps the most important caveat is time. As a relatively new form of vaccination, continued research and testing will be needed to better understand the benefits, drawbacks, and potential side-effects. Even still, the science so far points to an effective new weapon in the war of infectious disease.