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Preliminary data suggests Moderna’s mRNA flu vaccine is effective

Moderna, one of the pioneers of the COVID-19 vaccines and of mRNA vaccines, is now nearing a new breakthrough. The company recently announced results from its trial — and it seems to be safe and effective.

Digitally-colorized, negative-stained transmission electron microscopic (TEM) image depicting a number of Influenza A virions. Image credits: CDC.

With the ongoing pandemic, it’s easy to forget that influenza is also around — but it is, and it’s causing its own set of problems.

“Even before the COVID-19 pandemic, approximately three million people died each year due to respiratory infections, and many more are hospitalized or become ill as a result of these viruses,” said Moderna CEO Stephane Bancel in a statement hailing the result.

The problem with the flu is that it’s hard to make a vaccine for it. There are four main influenza viral variants (A, B, C, D), each with its own substrains, and influenza viruses, in general, mutate much faster than coronaviruses. In particular, the Influenza A virus is a fast evolver. This is why you have to take the flu vaccine every year: because it needs constant tweaking as the viruses change as well. The efficacy of existing influenza vaccines is around 40-60%, much lower than that of COVID-19 vaccines.

There’s another problem. The majority of current flu vaccines are based on inactivated viruses grown in chicken eggs. This means that you have to select the virus strains 6-9 months in advance. If a new strain were to appear in the meantime and you’d want to address that with your flu vaccine, you’d need to start over again.

But mRNA vaccines could change all that and make vaccines easier to develop (and hopefully, more efficient as well).

Before the pandemic, Moderna was already working on several mRNA vaccine candidates — of course, that had to be put temporarily on hold as resources were diverted to the COVID-19 pandemic, but Moderna hasn’t given up on its initial plans. It even announced it’s working on a double-whammy vaccine that could protect against the flu and COVID-19.

The Phase I clinical trials started in July 2021 and now, the first results are in.

Just preliminary results

The study was carried out on 180 people and produced high levels of antibodies in all participants, at all the dosage levels that were attempted (one of the main objectives of the study was to figure out the right dosage). Side effects were mild (mostly tiredness, headaches, and pain around the injection site) and were more likely to affect younger rather than older participants.

Moderna’s experimental flu shot is “quadrivalent,” meaning it focuses on four strains of flu: A/H1N1, A/H3N2, B/Yamagata and B/Victoria. These are believed to be the most prevalent and dangerous strains, according to recommendations from the World Health Organization.

However, Moderna is also working to include more strains in its vaccine. This is one of the main advantages of mRNA vaccines: they can encode defenses against different strains with relative ease. This is also why Moderna wants to mix its COVID-19 and flu shots into a single vaccine — they even want to include the respiratory syncytial virus (RSV), a common virus that causes the cold but can be threatening for infants and elderly people.

Yes, but

At first glance, this seems like good news. But analysts noted that the antibody results don’t appear to be better than that of existing influenza vaccines and in fact, appear to be somewhat inferior.

There are a few things to be said about the fine print of these results. For starters, the antibody response isn’t the only thing that drives the immune response — for instance, T cells also play a role — and these aren’t even interim results, they’re just Phase I trials. Phase I trials, sometimes called “first in humans” trials are meant to test the safety and zoom in on the right formulation and dosage, not to assess efficacy. Moderna expects results from Phase II trials in early 2022. Moderna also stresses that the main advantages of mRNA still stand: the benefit is that they can be produced quickly and customized on the fly based on what strains are prevalent in a specific year, and they can be combined with other vaccines into a single shot.

However, regardless of the results, This is a reminder that mRNA isn’t a magic fix for vaccines — or at least not yet. Immunology is like a hallway with many doors, and different doors require different types of keys; mRNA is one such key, but it’s not a master key that can open all doors, or if it is, we haven’t learned how to use it yet.

Moderna isn’t the only company in this race either. The mRNA vaccine technology went from being considered a distant possibility just a few years ago to one of the hottest topics in immunology, thanks to the success that the Pfizer/BioNTech and Moderna COVID-19 vaccines have enjoyed. Both Pfizer and BioNTech are working on their own mRNA flu vaccines, as are GSK (working with CureVac) and Sanofi (working with Translate Bio).

No doubt, we’ll be hearing a lot from these mRNA influenza vaccines in the near future, and there’s a good likelihood they’ll offer some improvement over existing vaccines. But for now, at least, mRNA isn’t shaping up to be a silver bullet.

Novel mRNA vaccine against ticks works in guinea pigs

A group of researchers from Yale University have developed an mRNA vaccine that teaches the immune system to identify saliva from tick bites. The vaccine, which proved to be effective in guinea pigs, could prevent ticks from feeding on and then transmitting tick-borne diseases to people, a growing problem in many countries. 

It's a much bigger problem than you think
Image credit: Creative Commons / Jaqueline Mattias.

The vaccine is based on the same mRNA technology that has proven effective against COVID-19. Essentially, the mRNA shot means being injected with genetic material from the target virus instead of the virus itself. The mRNA gives your body instructions to fight the targeted pathogen and then is eliminated. Researchers have been working on mRNA vaccines, but thanks to the great efforts invested in the current pandemic, we’re finally on the right path. 

“There are multiple tick-borne diseases, and this approach potentially offers more broad-based protection than a vaccine that targets a specific pathogen,” senior author Erol Fikrig and Yale researcher said in a statement. “It could also be used in conjunction with more traditional, pathogen-based vaccines to increase their efficacy.”

Lyme disease is the most famous and damaging of them all tick-borne diseases, but it’s not the only one. Lyme, as well as several other diseases, is expanding across North America and Europe, with about 40,000 reported cases in the US per year. Ticks are a potential danger to anyone outdoors, from farmworkers to hikers, and they transmit several pathogens that can cause serious health problems that can even be life-threatening.

The new vaccine is different from those developed by Valneva and Pfizer and it’s only early stages of development but moving forward. The main difference is that it targets the bacteria responsible instead of the tick carrier. They are both promising approaches that could bring a solution to a growing health concern. 

Developing a vaccine

The researchers at Yale developed a new vaccine that trains the immune system to respond to tick bites, exposing it to 19 proteins found in tick saliva. It has mRNA molecules that tell the cells to produce these proteins – just like the mRNA COVID-19 vaccine tells the cells to manufacture coronavirus proteins to shield against the virus. 

In a set of experiments, the team tested the vaccine on guinea pigs. Unlike unvaccinated animals, vaccinated guinea pigs exposed to ticks developed red rashes at the place where they were bitten, suggesting an immune response. The ticks also tended to detach early on without sucking as much blood as they normally would.

The researchers also placed ticks carrying the Lyme disease on both vaccinated and unvaccinated animals. They removed the ticks once the skin rashes appeared on the animals, something that usually happens in the first 18 hours. While none of the vaccinated guinea pigs became infected, half the unvaccinated animals did.

“The vaccine enhances the ability to recognize a tick bite, partially turning a tick bite into a mosquito bite,” Fikrig said in a statement. “When you feel a mosquito bite, you swat it. With the vaccine, there is redness and likely an itch so you can recognize that you have been bitten and can pull the tick off quickly.”

While the vaccine was successfully in guinea pigs, it wasn’t in mice – unable to get a natural resistance after infection. The researchers now plan to test it in other animals, such as rabbits, so to better understand how the immunity of ticks varies in different hosts, and slowly move on towards humans. They also want to develop in the future vaccines for other tick-borne pathogens.

The study was published in the journal Science Transnational Medicine.