mRNA vaccine technology moves to flu: Moderna says trial has begun

mRNA vaccine technology moves to the flu: Moderna Says Study Has Begun

Moderna has distributed the first doses of an mRNA-based influenza vaccine to participants in an early-stage clinical trial. announced the company on Wednesday.

Ultimately, Moderna plans to test the vaccine on approximately 180 people in the randomized, stratified, observer-blind phase 1/2 study. The study will examine safety, different dosages and immune responses.

The vaccine, called mRNA-1010, is designed to fight four lines of influenza virus that circulate seasonally each year, just like the current ones quadrivalent flu vaccines on the market. The four virus lines are those identified by the World Health Organization as those to be targeted each year for disease prevention – the seasonal influenza type A lines H1N1 and H3N2, and the influenza type B lines Yamagata and Victoria . If mRNA-1010 proves effective against the annual plague in later studies, Moderna intends to eventually bundle it with three other mRNA-based vaccines for an annual one-stop shot.

In addition to influenza, this proposed combination syringe would target two other common respiratory viruses that circulate alongside influenza:respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV) – as well as the COVID-19 coronavirus SARS-COV-2, the some experts have speculated that it could be seasonal. There are currently no approved vaccines against RSV or hMPV. And it is unclear whether SARS-CoV-2 will become seasonal and / or whether annual booster vaccinations will be required.

“We believe the benefits of mRNA vaccines include the ability to combine different antigens to protect against multiple viruses and the ability to respond quickly to the development of respiratory viruses such as influenza, SARS-CoV-2, and RSV” Moderna CEO Stéphane Bancel said in a statement. “Our vision is to develop a combination mRNA vaccine so that people can get a vaccination every fall to provide highly effective protection against the most problematic respiratory viruses.”

Vaccine design

While the company is aiming high with its seasonal megashot, the influenza component alone offers a significant improvement over current vaccinations. To the chagrin of mankind, the tetravalent and trivalent flu vaccines available for annual flu tend to be low in effectiveness, generally in the range of only 40 to 60 percent. In some years the vaccines are even less effective.

Moderna believes it can beat these numbers. The success of its mRNA-based COVID-19 vaccine – the one to be remarkable. would have 94 percent effectiveness in late-stage clinical trials—Moderna will target its more advanced, targeted mRNA vaccine platform to the fight against influenza. The company currently has three mRNA-based vaccine candidates in development. After mRNA-1010, there are mRNA-1020 and mRNA-1030.

In general, mRNA vaccines work by providing human cells with a portion of the genetic code of a virus in the form of messenger RNA (mRNA). This type of RNA generally acts as a mediator, conveying encoded instructions from DNA to the cell’s molecular machinery, which translates the code into proteins. However, the mRNA snippets in the vaccines provide the blueprints for viral proteins that the immune system can use for target practice. Once the cell’s machinery translates the vaccine’s mRNA code into a viral protein, the immune system uses that protein to train anti-virus antibodies and cellular defenses.

To prevent COVID-19, the mRNA vaccines contain the code for part of the SARS-CoV-2 spike protein. Copies of this protein stick out of the virus’ spherical body and help the virus enter human cells. As such, they are a simple and effective target for antibodies and other immune responses.

To prevent flu, mRNA vaccines could target key proteins that similarly stick out of the influenza virus, namely hemagglutinin (HA or H) and neuraminidase (NA or N). Like Spike, these proteins are critical to the flu virus’ ability to enter human cells. However, HA and NA come in different forms, represented in the names of the flu viruses as H and N (as in H1N1 and H3N2).

mRNA benefits

The mRNA-based vaccine strategy offers a highly precise method of combating HA and NA from influenza viruses compared to current flu vaccines, which are often based on the immune system of whole viruses, weakened or inactivated. And the mRNA-based design makes the vaccines easy to optimize. For example, if a flu virus showed up in one season with a slightly different version of HA – as it very often does – the vaccine coding might just need an update to adjust vaccination for that year. This is a change that could potentially be made quickly as well.

When variants of SARS-CoV-2 began to cause concern earlier this year, said the CEO of BioNTech, which worked with Pfizer to develop an mRNA-based COVID-19 that the company could customize his mRNA vaccine in just six weeks, if needed.

Perhaps the biggest advantage of the mRNA-based strategy over the current flu vaccine, however, is that it does not contain eggs. Current flu vaccines are mostly made from fertilized chicken eggs. Vaccine manufacturers inject the virus into the eggs and let the virus create legions of clones. Then vaccine makers harvest, purify, weaken, or kill the viruses and use them in vaccines. It’s cheap and easy, and it’s a method that has been used for decades.

But it’s also time consuming, requires lots of eggs, and may not produce highly effective vaccines. Weak or inactivated virus vaccines lack the precision of other vaccine strategies such as mRNA or recombinant proteins. With a whole virus, the immune system may attempt to attack many different characteristics of the virus, some of which may not be very useful in frustrating the invader.

Flu toll

In addition, humans are different from chickens. And sometimes influenza viruses can begin to adapt to their poultry conditions during the manufacturing process. This appeared to be an issue in the 2017-2018 flu season when a circulating H3N2 flu virus strain became too record a mutation in his HA in the manufacture of egg-based vaccines. The mutation may have improved the virus in infecting chicken eggs, but in the vaccine, the mutation appeared to cause people to develop antibodies that were not as good at defeating the H3N2 virus circulating in humans.

This flu season the flu vaccine had an overall effectiveness of. estimated only 38 percent. The effectiveness against type A influenza viruses, which also include H3N2, was only 30 percent. The 2017-2018 flu season ended with estimates of hospital admissions of up to 810,000 and deaths of up to 61,000 the worst of the decade.

Yet every year health professionals urge everyone to get the flu vaccine. The flu, as good as it sometimes appears, is a devastating infectious disease. Even a vaccine that is poorly effective can help. The CDC estimates since 2010, between 9 million and 45 million people have contracted influenza every year. In each of those years, they hospitalized between 140,000 to 810,000 people and killed between 12,000 and 61,000 people. In addition to the human cost, the economic burden of all of this is estimated at $ 11 billion a year.