The effect of mRNA influenza vaccine is not as good as inactivated vaccine

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The effect of mRNA influenza vaccine is not as good as inactivated vaccine

The effect of mRNA influenza vaccine is not as good as inactivated vaccine.

The COVID-19 vaccine has brought mRNA technology to the fore, and it has also made the market’s expectations continue to heat up.

The amazing mRNA technology, the prospects are by no means limited to preventive vaccines. The application of mRNA technology can be roughly divided into three areas: preventive vaccines, therapeutic vaccines and immunotherapy.

With the advancement of major pharmaceutical companies, mRNA technology is bound to bring us more surprises. But before that, pharmaceutical companies must accept many challenges.

In the flu vaccine race, mRNA technology has encountered certain difficulties.

A few days ago, the clinical data released by Moderna showed that compared with the inactivated vaccine, its mRNA influenza vaccine mRNA-1010 had a limited lead in targeting influenza A virus; for influenza B virus, the effect may not be as good as that of the inactivated vaccine.

If it is difficult for mRNA-1010 to produce impressive data in the future, its competitiveness will be greatly reduced. At any time, there is always a huge gap between the ideal and reality of new drug development that needs to be bridged.

The effect of mRNA influenza vaccine is not as good as inactivated vaccine

A faster, stronger flu vaccine

In the research and development of influenza vaccines, mRNA technology has been placed high hopes. The core reason is that mRNA technology is expected to bring about changes across the ages.

Currently, influenza vaccines include combinations of different technical routes such as inactivated whole virus vaccines, attenuated live virus vaccines, virion vaccines, and subunit vaccines.

Each technology has its own advantages, but also limitations. For example, inactivated vaccines have the disadvantage of poor protective effect, and the bug of subunit vaccines is that the production cycle is too long.

Compared with existing vaccines, mRNA influenza vaccines have the potential advantage of being “faster and stronger”.

“Faster” is reflected in two aspects.

One is the research and development end. Because of the convenience of the technology platform, the pace of early research and development of mRNA vaccines is relatively fast.

The most direct example is Moderna’s COVID-19 vaccine, which sent the candidate product into the clinical stage in just 7 weeks. In contrast, it takes about 3 months to complete this stage with traditional technology to manufacture influenza vaccines.

The second is the production side. From the process point of view, the manufacture of mRNA vaccines is simpler than recombinant protein vaccines, which helps to speed up the pace of vaccine approval and distribution.

For the development of influenza vaccines, “fast” is particularly critical, because influenza strains are prone to mutations, which will lead to uneven vaccine effectiveness. When the vaccine does not match the latest circulating strain, it may be only 10% effective.

The “fast” feature of mRNA technology may change this situation. Some market participants predict that a successful mRNA influenza vaccine may provide 40%-60% more protection than existing vaccines.

This also means that the mRNA flu vaccine will be stronger.

At the same time, compared with the existing technology, the antigen design of the mRNA influenza vaccine also has significant advantages, which can add more antigen combinations to improve the breadth and intensity of the immune response. In other words, mNRA influenza vaccines with excellent antigen design will have more prominent competitive advantages.

Based on the advantages of being faster and stronger, global vaccine companies have high hopes for mRNA influenza vaccines. Moderna, mentioned above, began Phase I trials of influenza mRNA vaccines in 2015.

However, at present, the development of mRNA influenza vaccine may not be as smooth as the development of COVID-19 vaccine.

Mixed data

In the competition for the COVID-19 vaccine, mRNA has shown amazing combat effectiveness, eclipsing the traditional technical route of inactivated vaccines. However, in the competition of flu vaccines, Moderna’s mRNA-1010 did not completely win the inactivated vaccine.

mRNA-1010 is a 4-valent influenza vaccine, which is expected to protect against influenza A H3N2, influenza A H1N1, and influenza B Victoria and Yamagata viruses.

The Phase III clinical trial of mRNA-1010 carried out by Moderna, the control group is the inactivated influenza vaccine Fluarix Tetra.

The interim results show that mRNA-1010 has an advantage in the seroconversion rate of influenza A H3N2 and influenza A H1N1 lineages, has an advantage in the ratio of neutralizing antibody titers to influenza A H3N2, and has an advantage in the ratio of geometric mean titers to influenza A H1N1 has non-inferiority.

This result means that, compared with Fluarix Tetra, mRNA-1010 has a potentially wider and higher protective effect against A-H3N2; against A-H1N1 virus, mRNA-1010 has a similar potential protective effect but a wider range of protection.

Although it did not crush Fluarix Tetra, the effect of mRNA-1010 is still good.

However, against influenza B virus, mRNA-1010 failed completely. Its seroconversion rate and geometric antibody titer against type B Victoria and Yamagata influenza viruses did not reach the non-inferiority results. That said, mRNA-1010 was not as effective as the inactivated vaccine.

Although, according to the National Institute of Allergy and Infectious Diseases, a multivalent influenza vaccine that protects against influenza A virus is the primary goal and that influenza B virus is a secondary goal, this still means that mRNA-1010 and inactivating Compared with the live vaccine Fluarix Tetra, the potential advantages may not be so obvious.

At the same time, mRNA-1010 had a higher proportion of adverse reactions. The results showed that the reported adverse reaction rate was 70% for mRNA-1010 and 48% for Fluarix Tetra.

The effectiveness data is mixed, and the safety data is at a disadvantage. The results of this set of data are not enough to meet the high expectations of the market for mRNA-1010.

After all, the world’s mainstream flu vaccine is Sanofi’s recombinant protein vaccine Flublok, which is more effective and safer than inactivated vaccines.

If mRNA-1010 cannot produce excellent data in the process against Fluarix Tetra, it means that it will be more difficult for it to challenge Fluarix Tetra.

On February 17, with the disclosure of clinical data, Moderna’s stock price fell by more than 5%, and finally closed down 3.31%. This may also indicate that the market does not have high expectations for mRNA-1010 at the moment.

The game has just begun

Of course, this does not mean that the prospects for mRNA technology in the field of influenza vaccines are bleak.

After all, as far as Moderna is concerned, mRNA-1010 is only one of five candidate influenza vaccines; for the entire industry, mRNA-1010 is only a representative of mRNA technology in the field of influenza vaccines.

As far as the current situation is concerned, better antigen design, or the use of adjuvants and other factors, all have the possibility of further achieving “faster and stronger” mRNA influenza vaccines.

With continued improvement, mRNA influenza vaccines still have the potential to revolutionize existing flu vaccines. You can understand that the vaccine revolution game driven by mRNA technology has just begun.

But at the same time, it further reminds us that setbacks and risks are the frequent visitors on the way forward for new technologies, even if there are super heavy products that prove that their technical routes are feasible, just like mRNA technology.

With the unprecedented success of the COVID-19 vaccine, market expectations for mRNA technology are at an all-time high. Paul Burton, chief medical officer of Moderna, predicted that the next decade will “see a revolution in mRNA therapy.”

In Paul Burton’s view, mRNA technology will become omnipotent, treating various diseases for patients around the world.

Moderna is also developing along this trajectory, and has built multiple pipelines with both abundance and breadth, such as preventive vaccines and tumor treatment vaccines.

In China, according to incomplete statistics, more than 10 vaccine companies have entered into the research and development of mRNA vaccines, including Aibo Bio, Aimei Vaccine, Sri Microbe, Lanque Bio, CSPC, CanSino, Shenxin Bio, Jiacheng Xihai, Neighbor organisms, Wiskin organisms, etc.

But now, the experience of mRNA-1010 undoubtedly tells everyone that mRNA technology is not a panacea. At least, it still has a long way to go before it becomes the all-powerful “savior”.

The effect of mRNA influenza vaccine is not as good as inactivated vaccine

(source:internet, reference only)

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