Delta booster?Updated vaccines to fight mutants are under test

When created by scientists mRNA vaccine In the case of Covid-19 last year, they were welcomed as an almost miraculous breakthrough. And it’s not just because the Pfizer / BioNTech and Moderna shots were surprisingly effective. mRNA technology was a radically new method for producing vaccines and had a major selling point. It will allow scientists to quickly represcribe vaccines in response to new mutants.

Which raises the question: where are our customized vaccines for the delta mutants that have devastated the planet for months?Where is that Plug & play Solution Have we been told to expect?

It’s a little late to come, so I’ll explain why later.But that’s for sure It’s not because mRNA technology is slower than scientists thought.

To understand why scientists are right to get excited, consider how mRNA vaccine production differs from traditional vaccine production. One of the reasons why vaccine production has traditionally taken so long is that scientists propagate many pathogens (or parts of them) in the laboratory and then introduce them into the human body so that the body can deliver the vaccine. This is because it needs to be recognizable.

For new coronaviruses, it is usually necessary to grow large amounts of coronavirus peaplomers (the parts of the virus that the virus uses to attach to human cells) in the laboratory.

Scientists have found a genius way to avoid this using the mRNA vaccine, Month. They identified the sequence of genes that make the peaplomer and used that set of “instructions” in the vaccine to urge our own body to produce the protein in the virus. These proteins stimulate the immune system.researcher Effectively Outsource work From their lab to our cells.

Using this method, scientists can easily modify the vaccine as needed. This is because it only switches the “instruction” of the old gene to the new set. (In January 2020, Moderna proved how fast this was. Designed the Covid-19 vaccine. One weekend!! ) Delta’s peplomer is very similar to its ancestral coronavirus, despite some mutations, so the new procedure does not need to be very different.

Now it’s A few Like it’s easy for pharmaceutical companies to mass-produce mutant-specific vaccines, It can be used as a booster for those who have already received two doses, or theoretically as the first dose for unvaccinated individuals.

And in fact, efforts to make delta-specific vaccines are in full swing. Pfizer / BioNTech and Moderna are included in the case, and these vaccines may be available in the coming months. But there is a problem here. You may not actually need it.

Delta-specific boosters are in clinical trials

A simple answer to the question “Where are the delta-specific vaccines?” It’s simple. Pfizer / BioNTech and Moderna already manufacture customized delta-targeted vaccines.

However, understanding how to make a bespoke peaplomer is only the first step. Currently, pharmaceutical companies are testing how well these modified vaccines work as boosters.

Pfizer / BioNTech is testing Represcribed vaccine candidates Especially targeting delta. The results of the clinical trial are scheduled for the fourth quarter of this year. Vaccines targeting beta mutants are also under investigation. (First identified in South Africa, Beta proved to be surprisingly proficient in avoiding immunityHowever, the super-transparent delta is now more dominant. “Both trials are in progress,” a Pfizer / BioNTech spokeswoman told me.

Similarly, Moderna recently Presentation Testing the represcribed vaccine Candidates to target beta and delta versions. The company has already begun testing three of the four candidates in Phase 2/3 trials to determine their effectiveness. In the coming weeks, we plan to start testing a fourth test (a combo candidate for both beta and delta). “Our strategy is to develop booster vaccines for mutants of current concern and those of potential future concern,” says Moderna. explanation In a news release for investors.

Delta-specific booster advances are good, but raise the question of whether they are needed.

Both pharmaceutical companies are also testing their original vaccine for booster efficacy. Pfizer, around that Second quarter financial reportFound that the third dose of the vaccine increased antibodies to Delta 5-fold between the ages of 18-55 and 11-fold between the ages of 65-85.

And according to Moderna Press releaseWhen the company tried a third dose of the original vaccine, the results were excellent. Antibodies to Delta increased 42-fold.

Antibodies are a signal that the human immune system can recognize and fight the virus and are not the only measure of immunity, but strong antibody numbers are a big sign.

These results are part of the reason some experts are uncertain. You need a delta-specific vaccine.Florian Kramer, a virologist on Mount Sinai Interview with doctor and researcher Eric Topol:

Testing of mRNA vaccines against beta mutants has been conducted in people who were first vaccinated with the usual mRNA vaccine. In some of these studies, the arm was given the same vaccine three times, with as much protection or good antibody against beta as well as against delta as the switched vaccine. It seems that you can get a level. Therefore, at this time, it is not clear if there is any benefit to changing the vaccine strain.

Dumbalouch, an immunologist at the Beth Israel Deaconess Medical Center in Boston The reason The delta-specific vaccine is probably not much better than the original vaccine, as delta’s peplomer protein is so similar in appearance and shape to its ancestral coronavirus. That is, the antibodies produced by the original prescription of the vaccine should work well to attack the virus when given a third injection.

Angela Rasmussen, a virologist at the University of Saskatchewan, agrees. “I don’t need a delta-specific vaccine,” she told me. Nothing has been shot yet, and even in the vast parts of the world where theoretically the delta-specific vaccine can be taken as the first dose, she is uncertain whether it is worth developing that conditioned vaccine. .. “Regulatory approval and manufacturing is time consuming and requires vaccines. now.. “

To mass-produce delta-specific vaccines and use them as the first unvaccinated dose, pharmaceutical companies take some manufacturing plants offline from the original vaccine production and start producing fine-tuned vaccines instead. There is a need, says infectious disease specialist Serene Gowner. Epidemiologist at NYU and Bellevue Hospital.Keeping them separate helps to avoid Unfortunate mistake, She added.

“Then it’s not proven that you really need to do that to protect yourself from the Delta, but is it really maximizing your manufacturing capacity,” Gonder said. “One is a manufacturing delay and you need to assign a specific manufacturing plant for that purpose. Two are FDA reviews that go into it, so there is a delay. Trade-offs mean trade-offs for delta variants. I don’t think it will. “

Was the RNA vaccine promise for Covid-19 exaggerated?

It is very helpful that the mRNA vaccine is produced faster than traditional vaccines and that the clinical trial process for fine-tuned mRNA vaccines is shorter than the original vaccine. However, it still takes months to reconstruct the vaccine during testing, manufacturing, and regulatory approval.

Does that mean that the first optimism about mRNA adaptability was exaggerated?

“I think optimism is great except in the urgent Covid era — this is [mRNA technology] It may facilitate the long-term development of vaccines. Great for seasonal flu, which already has a process to quickly evaluate the prescribed vaccine! “Rasmussen said. “But in the urgent situation we are currently facing at Covid, the regulatory process is still taking a long time and we don’t have it so far.”

In other words, all the incredible technologies (and arguably mRNA is an incredibly world-changing technology) are all working well, but only in scenarios where regulatory pathways allow vaccine regulation. You can maximize your potential. It was evaluated efficiently.

Gounder doesn’t think it needs a delta-specific vaccine, [the drugmakers] To move this forward, even if that particular reform isn’t widely used, “she said. “It really helps them understand what the problem with updated vaccines is in terms of manufacturing issues and regulatory pathways.”

“It’s like a practice run,” she said, given that mutations that dramatically escape our vaccine can still occur.

As a Pfizer / BioNTech spokesperson said in an email:

The study is aimed at studying mutants and should enable companies to respond quickly if escaped mutants require the latest vaccines. The two companies are exploring the development, manufacturing, and regulatory pathways BioNTech and Pfizer will pursue in this case so that the vaccine can be applied within 100 days if needed. This approach is part of BioNTech and Pfizer’s comprehensive strategy for addressing variants in the event of future needs.

According to Boston University epidemiologist Benjamin Linas, there is another reason why making a re-prescribed vaccine to fight Delta may have made a late start. There are many unused doses of the original vaccine, and public health officials and pharmaceutical companies may have feared it would be wasted if people decided they only wanted a “new and improved” version. not.

“I don’t know what message it will send [Pfizer or Moderna] “Oh, there are vaccines specially designed for Delta.” Does that raise concerns that the original vaccine didn’t work? This is absolutely not true, “Linas said. Said.. Vaccines are still really effective against Delta, especially in preventing serious illness and hospitalization.

A delta-specific vaccine may be offered this winter.But it is No It means something is wrong with the original vaccine — and Those who are currently eligible for boosters and have been waiting at least 6 months after the second dose should remember that the original vaccine is fully functioning as the third dose.

“This is especially true for people at high risk,” Rasmussen said. “They need to get a third shot right now instead of waiting.”

FDA and CDC approved Give booster shots to some Americans who have been vaccinated with Pfizer / BioNTech, that is, people over the age of 65 and residents of nursing homes Medical condition It increases the risk of severe Covid-19, and those who work are at increased risk of getting the virus.