Does omicron vaccine protect against BA.5?: Why the vaccines are lagging behind the virus

Moderna reports first successes with the specific vaccine against the omicron variant.

Does omicron vaccine protect against BA.5?: Why the vaccines are lagging behind the virus

Moderna reports first successes with the specific vaccine against the omicron variant. However, the rapid spread of the BA.5 subtype clouds the promising prospects. Because it seems that the adapted vaccine will not be able to stop a BA.5 wave.

The omicron subvariant BA.5 continues to spread in Germany. The Robert Koch Institute (RKI) now estimates their share at ten percent. But: The number refers to the week before last. If the doubling of the past few weeks has continued, it should currently be around 40 percent. Experts assume that BA.5, as in Portugal, will displace the previous virus types in the shortest possible time. The RKI warns that “an increase in the number of infections and a renewed increase in infection pressure on vulnerable groups of people” can be expected in the summer.

Meanwhile, hopeful news is coming from the pharmaceutical industry: The US company Moderna recently reported that it was able to achieve an improved immune response against Omikron with a mixture of an old and an updated vaccine. And Biontech is also currently developing a vaccine adapted to Omikron. The problem is that these will probably not come onto the market until autumn and are primarily adapted to old Omicron types, such as the BA.2 variant, which is currently still dominant in Germany.

BA.5 has a mutation in its genome that did not yet exist in BA.1 and BA.2: L452R. At position 452 of the spike protein, one amino acid building block has been exchanged for another. Apparently, this mutation increases the transmissibility of the virus. Another mutation, F486V, may also be responsible for BA.5 being able to partially evade the immune system. This makes infection with this subvariant more likely.

Does the Omicron Booster still protect? Or has the corona virus mutated so badly with BA.5 that a BA.1 or BA.2-specific booster is already out of date? A new study by Biontech researchers, published in the journal Science Immunology, suggests that this could actually be the case. According to this, those who had been vaccinated twice and three times with Biontech/Pfizer gained hardly any additional neutralizing antibodies against BA.4 and BA.5 as a result of a breakthrough infection with Omicron BA.1.

The vaccine breakthrough led to a growth in antibodies against all previous variants including BA.1. However, compared to the new lines BA.4 and BA.5, the values ​​were similarly low as in those who had been vaccinated three times without a vaccination breakthrough. The values ​​were also about six times lower than against the original Wuhan virus.

The researchers led by Jasmin Quandt assume that certain immune mechanisms are the cause. In the event of a vaccine breakthrough, for example, those antibodies that are directed against regions of the virus that have not changed between the variants are strengthened. However, completely new B cells that produce antibodies are rarely formed. If new variants then appear in which the previously preserved regions have changed, these antibodies are also less effective.

It would therefore come as little surprise to Sebastian Ulbert if virus evolution continued to outpace vaccine development. "If a virus like Sars-CoV-2 circulates in a pandemic, you will always lag behind in vaccine development, even with flexible technologies such as mRNA vaccination," said the senior immunologist at the Fraunhofer Institute for Immunology and Cell Therapy (IZI) the MDR. This is because the vaccines are very specifically tailored to certain surface structures of the virus, especially the so-called spike protein. If these change through mutation, the vaccines are no longer as effective. This will be even more true as future variants perhaps feature even bigger changes.

"It turns out that the current method of adapting the vaccine is too slow," explains virologist Sandra Ciesek. Up to now, the adapted vaccines have had to be checked for their effectiveness before they are approved. This is a lengthy process.

The annual approval of influenza vaccines shows how things can be different. Here the evolution of the virus is observed worldwide and the vaccine is adapted every year without the need for new efficacy studies for approval. "Maybe we have to get there with Sars-CoV-2 if really only the sequence of the spike is adjusted," says Ciesek.

Even if the omicron booster against BA.5 does not achieve the desired effectiveness, the development of such adapted vaccines still makes sense, emphasizes immunologist Reinhold Förster from the Hannover Medical School. "It may be that at some point a pi, rho or sigma mutant will appear against which, for example, the adapted Omicron BA.2 vaccine suddenly shows an excellent effect," he told the "world". That's why you have to develop as many different vaccines as possible. "Because then at some point you just have to open the drawer and hopefully be able to say: Yes, vaccine twelve should actually work well against the new Pi mutant," says Förster. Something like this could be tested very quickly in the laboratory.

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