Pharmaceutical laboratories are researching new applications for mRNA vaccine technology — and Moderna is hoping to integrate COVID-19, influenza and respiratory syncytial virus immunization into a single jab.Credit: Adam Glanzman/Bloomberg via Getty
A single vaccine has been shown to protect people from both SARS-CoV-2 and influenza viruses — and with a higher effectiveness than vaccines that target one or the other, the pharmaceutical company Moderna has announced.
Moderna, which is based in Cambridge, Massachusetts, said earlier this month that it had successfully completed phase-III clinical trials for the drug, which — like the company’s pioneering COVID-19 vaccines — is based on mRNA. In a statement to its investors, Moderna said that the vaccine was more effective at providing immunity to adults over the age of 50 than competing flu and COVID-19 shots.
Moderna is now planning to seek approval from the US Food and Drug Administration (FDA) to bring the vaccine to market.
Combination vaccines can have big public-health benefits, but they are often time-consuming and expensive to develop. Moderna’s latest rapid success shows that RNA can help to overcome some of these difficulties, says James Thaventhiran, a clinical immunologist at the University of Cambridge, UK, “This is a great example of why the technology is exciting,” he says, adding that the combination vaccines using mRNA are “just the beginning” for RNA technology.
The RNA effect
Vaccination helps people to build immunity to a disease by exposing their immune cells to an antigen, such as a protein, a snippet of DNA or even a whole pathogenic organism that has been inactivated. When the real pathogen comes along, the immune system is quickly able to recognize the threat and mount a resistance.
Creating antigens is a difficult process, and combining different antigens into one vaccine increases its complexity further. “It sounds like it should be so easy, right? You just mix them together,” says Jacqueline Miller, a paediatrician and head of development for infectious disease at Moderna. “But it’s actually much more complicated than the development of individual components.”
The chemical components that make up single-target vaccines can sometimes react with one another when combined, running the risk of making the individual drugs less effective. mRNA-based vaccines don’t face as much of a hurdle, however, because the drug components for different antigens tend to be the same.
mRNA is a molecule made of nucleic acids, and its main purpose is to tell cells what proteins to make. mRNA-based vaccines inject mRNA into cells to make copies of antigens for the immune system to recognize. So, rather than having to make a bunch of different components, mRNA vaccines simply wrap up a set of instructions in a layer of lipids and then send them into the body for cells to pop out their own antigens.
The result is a strong immune reaction based on drug components that don’t compete with one another — even if they are targeting different pathogens.
That might explain why the risk of combination vaccines being ineffective is “clearly” not a problem with the new COVID-influenza vaccine, says Thaventhiran, because the shot seems to boost immunity more than single immunizations do.
The vaccine’s code can also be quickly changed to keep up with evolving variants. One of the issues with current, non-mRNA influenza vaccines is that the antigen is grown in chicken eggs, a process that takes six months. During that time, the virus can mutate and change. By contrast, “with RNA it literally takes weeks to make a new variant”, says Drew Weissman, an immunologist at the Perelman School of Medicine University of Pennsylvania in Philadelphia.
Modern mRNA immunization
Researchers have been testing the limit for the number of antigen instructions they can fit into an mRNA vaccine; one group has fit mRNA instructions for all 20 variants of influenza into a lipid layer1. Moderna is hoping to add the respiratory syncytial virus (RSV) — which causes cold-like symptoms — as a third pathogen to its current COVID–influenza pair.
For most people, FDA approval of the Moderna shot “means one visit to the pharmacy”, says Weissman. “One shot will be enough to protect you from both the flu and COVID.”
COVID-19 booster uptake has dropped in the United States since the first rounds of vaccinations. However, as of this year, around 47% of adults have received the flu shot, according to the US Center for Disease Control. Combining immunizations could help to ensure that more people are protected from COVID-19, says Miller.
And looking forward, mRNA combination vaccines could help to reduce the burden of immunizations for parents of young children. Infants are currently the primary targets of available combination vaccines, but they are still given multiple rounds of shots in the first few years of their lives. “Parents would be ecstatic” to reduce the number of shots their children must get, says Weissman. And having just a few shots — which could be administered at the same time — would also help to ease that burden of immunization in rural communities in low-income countries.
Researchers will have to work out how to deal with the delicate nature of mRNA to see these benefits expand outside of high-income nations, says Thaventhiran. Part of the challenge of rolling out COVID-19 vaccines was the need to keep doses in deep freeze to protect the mRNA from breaking down.
But overall, the development of mRNA combination vaccines is evidence “that RNA has a positive future”, says Weissman. “It isn’t just a fluke.”
