How COVID-19 vaccines can cause new vaccines against other deadly viruses

Vaccination has come a long way since Dr. Edward Jenner used pus from an infected bottle to create the first smallpox vaccine in 1796. However, vaccines have almost always used some of a pathogen itself. same, until COVID-19 incorporated emerging technology into the spotlight. Now, some experts predict that the technology will lead to new seasonal flu vaccines for HIV.

The technology is based on messenger RNA, a molecule that carries the genetic code; they trust the two COVID-19 vaccines authorized for emergency use in the US. Created separately by Moderna and a collaboration between Pfizer and BioNTech, both vaccines were developed in a few days and both were shown to be highly protective in clinical trials. (Learn more about how mRNA vaccines work).

Some experts believe that mRNA vaccines are the key to faster or more effective vaccine programs, to fight multiple viruses with a single shot, or to provide protection against difficult diseases.

“Technology has been shown to be safe and effective and everyone on planet Earth knows it, except anti-vaxxers,” says Derrick Rossi, a biologist and biotech entrepreneur who co-founded Moderna and has since left the company. “But I drank Kool-Aid a long time ago.”

In January, Moderna committed to new programs to develop mRNA vaccines against the Nipah virus, HIV, and influenza, adding to its vaccine pipeline that already included more than 20 mRNA efforts. Pfizer is also working on additional mRNA-based vaccines, including one for seasonal flu, says Phil Dormitzer, the company’s scientific director and vice president of viral vaccines. Dozens of other manufacturers and labs around the world are working on similar efforts.

But while it is tempting to view technology as a kind of scientific savior, some experts warn that only so much can be extrapolated from the success of COVID-19 vaccines and that mRNA will not answer all vaccine prayers. . Here it is explained how experts think that mRNA could change the landscape of vaccines in the future and the numerous obstacles they will face as they develop.

Traditional vaccines use weakened viruses or fragments of viral proteins to teach the immune system to recognize and fight an invader. Scientists bet that mRNA could teach the same lesson, if only it could get it stuck. When used in a vaccine, mRNA is a mobile molecule that provides instructions to our bodies to make the components of a virus that trigger an immune response. But it’s a temporary message: the body quickly degrades mRNA after reading it, a problem for scientists who wanted to use it in vaccines.

Drew Weissman, a professor of medicine at the University of Pennsylvania, and Katalin Karikó, biochemist of Pfizer’s COVID-19 vaccine and BioNTech, helped solve this puzzle in 2015. His team discovered that the mRNA surrounding a coating of lipid nanoparticles not only provided the message produced a vaccine adjuvant, a substance that promotes the production of antibodies. (Also learn about scientists who spent 12 years unlocking another vital part of the first authorized mRNA vaccines for human use.)

With this delivery system, mRNA vaccines can teach our bodies how to make and fight a viral protein without ever encountering the pathogen. In addition, the same basic ingredients can be used each time, adding only a single component, an mRNA sequence, to produce the necessary protein.

In COVID-19 Moderna and Pfizer-BioNTech vaccines, this ingredient is the sequence that encodes the coronavirus’s flagship protein, which is what allows the virus to enter human cells. In theory, you could trade this sequence of cutting-edge proteins for one that makes an HIV antigen and you would have an HIV vaccine, Weissman says. Finding the right protein is the challenge, but the method is always the same. “That’s why they call it‘ plug and play, ’” he says.

With mRNA, scientists can go from “discovering the sequence of the virus to having something in a vial in a matter of weeks,” says Anna Durbin, a professor of international health at Marys Hopkins Bloomberg School of Public Health in Maryland. Modern, for example, created her COVID-19 vaccine two days after obtaining the sequence. And following the clinical successes of this technology, scientists are redoubled efforts to create mRNA-based vaccines for other diseases.

Weissman’s lab is working on about 30 mRNA vaccines, he said, including a universal flu vaccine that would work against all strains of the flu and a pan-coronavirus vaccine that would fight all coronaviruses, from severe acute respiratory syndrome. (SARS) to Middle East Respiratory Syndrome (MERS).

Weissman says mRNA vaccines could even fight multiple pathogens in a single shot by targeting so-called conserved sequences, portions of viral genomes that do not mutate at all or so quickly and are consistent between multiple pathogens and their variants. Conserved sequences do not usually elicit an immune response, which is why some previous vaccines have not been effective against them. For example, flu vaccines target hemagglutinin, a protein made from a head and a stem. Influenza vaccines elicited immune responses against the rapidly mutating head, but not against the preserved stem.

But thanks to the adjuvant that mRNA creates when surrounded by lipid nanoparticles, it is able to target and create a strong immune response against the stem, Weissman explains.

If successful in human clinical trials, the universal Weissman flu vaccine could mean one vaccine every decade instead of every year, he says. And some scientists, including Weissman, believe that because mRNA can elicit potent immune responses against parts of viruses that are usually less sensitive, these vaccines could also hold the key to hitherto insoluble puzzles, such as HIV.

But mRNA vaccines are hardly a “magic bullet,” Dormitzer warns. And they will face many obstacles, according to some experts, before they can become dominant and accepted by the masses.

The Pfizer COVID-19 vaccine, for example, should be stored at -70 ° C, a much colder temperature than some health centers can accommodate. This is because of the lipid nanoparticles used to administer mRNA, Weissman says. Lipid nanoparticles are like fat: when a droplet of fat is kept, it keeps its shape. But when the fat drops are left or heated, they liquefy and combine. Lipid nanoparticles do the same thing and once they do, they don’t work.

Other scientists are working on different delivery systems that avoid lipid nanoparticles; Pfizer and Weissman labs are working on mRNA lyophilization vaccines, which Weissman says could allow them to be stored in the refrigerator or even at room temperature. But it is an expensive process and ensuring that it works takes a long time.

“To know that something is stable in the fridge for a year, you have to put it in the fridge for a year and wait,” Dormitzer explains.

Scientists also do not yet know how long the immune response will last after receiving an mRNA vaccine. But the Pfizer-BioNTech COVID-19 vaccine was the first of its kind authorized outside of clinical settings, so scientists simply do not have enough data from clinical trials.

COVID-19 vaccines have also caused some uncomfortable reactions. For example, about 90 percent of people report arm pain after receiving the vaccine, compared with about 60 percent of people who have arm pain after receiving a flu shot. These mild reactions may be tolerable in a pandemic, Durbin says, but they may be less acceptable outside of crises or for less threatening pathogens. “We have enough difficulty vaccinating people for the flu now,” he says.

More worrying are the anaphylactic reactions that some people experience after receiving a COVID-19 vaccine. Just over two out of every million people who have been shot by Moderna experienced anaphylaxis, a severe and life-threatening allergic reaction, while Pfizer and BioNTech reported about 11 cases of anaphylaxis for every million dose of your vaccine. Statistically speaking, the risk is low and manageable. But it is still higher than for other vaccines, and the reactions can be caused by lipid nanoparticles, things that allow mRNA to enter the body without degrading.

Nicole E. Basta, an associate professor and epidemiologist of infectious diseases at McGill University in Montreal, says people often value the risk and benefit when deciding whether to get vaccinated. For COVID-19 vaccines, their high efficacy (up to 95 percent in the Pfizer vaccine and approximately 94 percent for the Moderna vaccine) should tip the balance toward risk and benefit, he says. she.

And while new technology often means that changing or conflicting information comes out quickly, Basta says it provides a unique opportunity for scientists to help people feel more comfortable with technology and understand it better.

“I really encourage people to keep an eye on what’s going on in the vaccine field, because vaccines are most beneficial when a lot of people get them,” he says. “I think the discourse and discussion about mRNA vaccines is a really positive thing for public health and I hope this will improve confidence in vaccines.”

While the technology is promising, Pfizer’s Dormitzer wonders if mRNA will be the troubleshooter many believe.

“There are some diseases that are really susceptible to vaccination,” he says, and includes SARS-CoV-2. “Others are pretty tough. The flu is hard. And some were quite impossible until now, “including HIV and hepatitis C. Some viruses may be impervious to technology. Other vaccines are just as effective now, such as the measles, mumps, and rubella (MMR) vaccine. that Dormitzer says it would make no sense to change them.

Whether or not mRNA vaccines become the vaccines of the future is one thing for sure: the next ones to hit the market will not be developed as quickly. Although COVID-19 vaccines were created at record speeds, “the severity of the pandemic really put the gas pedal on these products,” says Rossi, who is no longer affiliated with Moderna.

The crisis also removed several barriers to typical vaccine production, as each manufacturer prioritized the same goal and many conducted phases of clinical trials in parallel, rather than a few years apart. Previous mRNA vaccines had already been given to other viruses, including coronaviruses, although they have not been released.

“What people need to realize is that we’ve been working on mRNA for 15 years and mRNA vaccines for eight years,” Weissman says.

Dormitzer says there are lessons that vaccine manufacturers can learn from the pandemic, such as modifying their processes to make trials more concerted or more efficient. “I think we can do some acceleration,” he says. But not all scientists will be focused on a single vaccine going forward.

“We will return to normalcy and have our normal range of interesting concerns,” he says. “And so things won’t be like that, nor would we want them to be like that.”