The use of mRNA vaccines also has the advantage of protecting against flu. The first approvals for the preparations will be submitted soon. But researchers also point out weaknesses.
Conventional flu vaccines are largely produced using chicken eggs – the use of faster-to-produce mRNA vaccines is now approaching. The Pfizer Group has presented the results of a pivotal phase III study of its mRNA flu vaccine. It prevents more flu cases than conventional vaccines and triggers a stronger immune response, according to the New England Journal of Medicine. However, vaccination reactions also occur more often.
The mRNA vaccination technology allows rapid adaptation to new variants in the manufacturing process, explained Alexander Dalpke of Heidelberg University Hospital, who was not involved in the research. Such adjustments are required every year for seasonal influenza.
In addition, the technology is easy to develop – this is not the case with conventional vaccines made from chicken eggs. Rapid adaptation and scaling will be critical in the event of a new influenza pandemic, said Dalpke, who is a member of the Permanent Commission on Vaccination (Stiko).
Flu epidemics occur annually in the colder months – in the northern hemisphere from October to March, in the southern hemisphere from April to September. The most common pathogen is the influenza A virus, which is divided into many subtypes according to its surface proteins hemagglutinin (H) and neuraminidase (N). Small changes in this protein continue to create new variants in circulation, so the vaccine is adjusted every year according to WHO recommendations.
Vaccine production takes six months
Currently, vaccine strains for vaccines in the Northern Hemisphere must be determined in February, as vaccine production takes about six months, explains Florian Krammer from the Medical University of Vienna. “At this time, influenza season is occurring in the Southern Hemisphere and changes in viruses may occur.” This could mean that a particular vaccine is no longer compatible with circulating strains, reducing its effectiveness.
“These mRNA-based vaccines can be produced more quickly; a decision on the type of vaccine does not need to be made until May or July,” Krammer said. Thus, there is already data from the Southern Hemisphere and the possibility that the resulting vaccine will match the circulating virus will be much greater.
If an mRNA flu vaccine is approved, this would also provide an advantage with respect to potential pandemic influenza: If a company already has an approved seasonal influenza vaccine on the market, then it can quickly transition to that pandemic strain without conducting lengthy efficiency studies, such as those required for Covid-19.
Pfizer is testing its vaccine in the US, Philippines and South Africa during the 2022/23 flu season. In phase III studies, the safety and effectiveness of a drug or vaccine are tested on a large number of test subjects. The results provide important data for regulatory authorities to assess whether the vaccine is safe and effective enough for widespread use.
In the Pfizer study, more than 18,000 people between the ages of 18 and 64 received either the mRNA vaccine or the traditional vaccine. The relative effectiveness of the mRNA vaccine compared to the control vaccine was 34.5 percent: There were 57 illnesses in the mRNA group and 87 illnesses in the control group. The majority of cases are influenza A cases.
According to the data, the immune response to vaccination in the blood was noticeably stronger in the influenza A strain and similar or lower in the B strain. As is common with other mRNA vaccinations, there were more vaccination reactions, most of which were mild to moderate and only temporary. At the one percent level, serious side effects are as common as conventional drugs.
Better effectiveness versus increased side effects
The increase in vaccination reactions is similar to that known for the Covid-19 vaccine, explained Dalpke. “This is not inconsistent with approval – if used there would be a trade-off between greater effectiveness and increased side effects.”
Before Pfizer, the company Moderna had presented the results of a phase III study for its seasonal mRNA flu vaccine mRNA-1010. The immune reaction to this is no less than conventional vaccination, and side effects occur more often. According to Moderna’s announcement, mRNA-1010 also prevented more influenza illnesses than the control vaccine. However, these results have not been published in a specialist journal.
The two mRNA vaccines are similar, Krammer explained, and both showed good effects and slightly higher efficiency than conventional influenza vaccines. “Side effects are higher, but you can accept them – especially in at-risk groups – for better protection.” However, it should be remembered that there are already better vaccines for risk groups based on standard technology. There is currently no direct efficiency comparison with preparations from Pfizer or Moderna.
In addition to the phase III studies presented, Dalpke pointed out that it is still unclear whether there is fundamentally better effectiveness than conventional vaccines or perhaps only in the season under consideration. However, in general, mRNA vaccines can also be produced for influenza and are effective. The general effectiveness of mRNA technology has been confirmed.
Annett Stein, dpa/wb
