Is there a single antimutation vaccine for Covid? | Vaccines and immunity

THis week government announced Additional Vaccine Booster Jab It has been suggested that people over the age of 75 are likely to need more shots in the fall. But imagine if the next Covid Vaccine Jab you have was the last one you’ve ever needed. It is possible to create a “universal” vaccine against the Sars-CoV-2 virus that works well against all existing variants as well as against those that the virus is likely to mutate. It is a dream that is being actively pursued by researchers who believe that it is. future.

Some people are thinking even bigger. In January, Joe Biden’s chief medical adviser, Anthony Fauci, and two other experts said that “universal” works against Sars-CoV-2 as well as many other coronaviruses in potential animal populations. We called for further research on the coronavirus vaccine. It spreads to humans and causes future pandemics. “We need a research approach that can characterize multiple species of the global’coronavirus universe’,” Fauci and colleagues said. Written in New England Journal of Medicine“And apply this information to the development of” universal “vaccines that provide widespread protection for all. [coronaviruses].. “

Is it just a fantasy? necessarily. After all, when the pandemic began, many thought it was fancy for us to vaccinate against Covid-19. In less than a year.. However, experience has proven that “as a research community, we can do amazing things together,” said Larry Corey, a virologist and vaccine expert at the University of Washington in Seattle. Says.

Current vaccines have been developed against the original “ancestral” mutant of Sars-CoV-2. Corey also told Delta that there seems to be a 90-fold difference in mortality between vaccinated and unvaccinated people. However, the Omicron variant transmitted faster than other variants and aroused caution due to its ability to infect vaccinated people. Very few people develop serious symptoms from Omicron, but vaccination (and natural infections) can actively suppress the activated immune defenses.

Variants acquire changes in the chemical structure of viral proteins through random mutations as the virus replicates. This gives you a competitive advantage. For example, the transmission rate is improved. Many of these changes occur in so-called spike proteins. Peplomers stick out of the virus’s shell and latch into proteins in the membrane of human cells, creating attachment and attack points.Omicron An amazing number of such mutationsShows the capacity required for Sars-CoV-2 to bring surprise.

One answer is to adapt the vaccine to the mutant. The mRNA vaccine created by Pfizer / BioNTech and Moderna contains an RNA molecule that acts as a cell template for creating harmless fragments of the spike protein. It is a vaccine antigen that stimulates the immune system to recognize viral proteins and find antibody molecules that mobilize immune cells against them. Then, if a real virus invades our body, our immune system is ready to identify and destroy it. Other vaccines, such as AstraZeneca, use other methods to induce the same immune priming. If the structure of the peaplomer of the variant is slightly different, in principle, the RNA molecule can be modified to encode a portion of this new protein.

As is widely expected, Sars-CoV-2 eventually becomes endemic within the population and is constantly circulating at low levels, such as influenza and cold viruses, but can cause epidemics. In some cases, the vaccine can be tailored to the current variant. Circulation. This is more or less what happens with influenza: each season’s flu vaccine is based on the best guesses about what the seasonal strains are likely to be.

This is all working very well. However, Omicron shows how quickly a very new variant of the coronavirus can emerge and spread around the world. Pfizer and Moderna are now Vaccine tailored to Omicron.. But even if you could create and test this within a few months, it could be too late. Therefore, a universal vaccine that can protect against all variants may be desirable. Kayvon Modjarrad, head of a team exploring vaccine development at the Walterlead Army Institute in Silver Spring, Maryland, said:

AThe moment when there is no panvariant vaccine against endemic virus. Researchers have long dreamed of a universal vaccine that makes the flu epidemic less deadly. There are now promising signs that it is possible.. The design principle of the Universal Covid Vaccine follows a similar policy.

One option is to prime the immune system to recognize many bits, not just one bit of viral protein. All of these are unlikely to change (or significantly) at once in the new variant. It provides the immune system with different ways to find and control intruders and expect them to work. This may include, for example, the creation of an mRNA vaccine containing many different RNA molecules, each encoded as a different protein fragment. Alternatively, a single particle in the vaccine may carry several different fragments.

Alternatively, you can look for parts of the virus that appear to be “saved” between variants. Perhaps such changes are too harmful to the virus and are proteins (or some of them) that do not mutate at all. But how can you tell what happens to variants that haven’t appeared yet? One way is to see if highly conserved protein regions already exist within the entire family of related coronaviruses. “If you can find something in common with Sars-CoV-2, Sars [the related respiratory virus that caused alarm in 2003]When If there are many other animal coronaviruses, they may also be included in the following variants of Sars-CoV-2, “said San Francisco-based Vir Biotechnologies, which is working with GlaxoSmithKline on vaccine development. Chief Scientific Officer Skip Virgin said. – Collaborations that have already been created Monoclonal antibody sotrovimab To relieve the symptoms of Covid.

Currently, researchers are primarily striving for a relatively modest goal of attacking only a subset of the coronavirus world. This is because it stimulates an immune response to some of the spike proteins, usually called receptor binding domains (RBDs) shared by Sars. , Sars-CoV-2 and closely related bat coronavirus. RBD is part of the spike protein that latches into the host cell. Some variants have small mutations in RBD, but their chemical structure does not change much. It should create a strong immune response against RBD and work against this family of viruses.

The Modjarrad team has started Phase I clinical trial Of their pandemic vaccine in April 2021 (only looking at safety). It uses small nanoparticles called ferritin-a natural protein that stores iron atoms in the body-many copies of Sars-CoV-2RBD are studded.

It has long been known that many copies of the antigen in a single vaccine particle elicit a stronger immune response than a single copy. The institute is keen to publish details of its progress until the clinical trial data is released.However, in December Results announced by the team Their ferritin vaccine has been shown to provide Makaku with excellent protection against not only the ancestral form of Sars-CoV-2, but also Alpha, Beta, Gamma, Delta variants, and the original Sars virus. ..

Barton Haynes of Duke University School of Medicine in North Carolina takes a similar approach with RBD-studded ferritin-based nanoparticles.May last year he and his colleagues Reported candidate vaccine Protected macaques from bat coronaviruses such as Sars-CoV-2, Sars, and some Sars.Most recently they have shown that it produces Good immune response Also for Delta and Omicron variants.

Haynes says he hopes to begin clinical trials in humans at the end of 2022. If they do well, I think it could take a year or two before the vaccine becomes available. Guarantee another large phase III clinical trial before approval.

These efforts may result in a vaccine resistant to all SARS-CoV-2 variants, but in principle such an approach is broader and the universal corona sought by Fauci et al. We provide virus vaccine. Haynes says it will probably involve finding RBDs that are important to other families and adding them to the particles. That is the beauty of the nanoparticle approach. It can easily incorporate various protein fragments into so-called multivalent vaccines.

Finding the right protein fragment can mean combing thousands of coronaviruses Known to infect wildlife In addition to bats, civets, and raccoon dogs, there are also four coronaviruses that are already endemic to the human population and cause respiratory symptoms such as the mild cold. It will be a big job. But now that the terrifying dangers posed by the coronavirus (including those that caused the Sars in 2003 and the Mers outbreak in 2012) have been discovered, investment is with the economic and social harm it can prevent. It is cheaper than that. Haynes hopes that one jab could protect against all coronaviruses for 5-10 years.

Of course, no one can be sure what the horribly original Covid-19 virus has for the future. “The first axiom of infectious diseases never underestimates the pathogen,” says Corey. “The speed with which we get four major variations in two and a half years is unprecedented and amazing. We won’t bet on this virus.”

But even viruses have their limits. For example, despite a wide set of mutations in Omicron, Vir’s sotrovimab still works against it. “Viruses can change some things, but it’s really hard to change others,” says Virgin. “There are some things you can’t escape when a virus changes.” If you can find them, you’re in business. “I’m optimistic that we can produce a vaccine that offers a truly wide range of protection,” he says.

Even current vaccines are still successful in preventing death, and we are also building antiviral and other therapeutic weapons. More important now, according to Corey, is a vaccine that is more effective against all mutants in stopping the infection. “We see that the structure of our lives, our travels, and the things that make up modern culture are greatly hampered,” he says, even when mortality declines. Therefore, we need a second-generation vaccine that can prevent widespread infections. This is what Corey says is widely regarded as a tougher goal and will be difficult to assess until it is deployed.

It’s tempting to think that this pandemic needs to be resolved before it’s ready for the next pandemic, but “there’s no reason why a pandemic reaction can’t prepare for the next pandemic,” says Virgin. And in the end, he adds, it’s easier to persuade the government to spend on solving existing problems than problems that haven’t happened yet.

“We want to get to the point where we’re preventing the next pandemic, rather than responding to it,” says Neil King of the University of Washington in Seattle. Also under development A universal nanoparticle-based coronavirus vaccine. “The only way to do that is to use a broadly defensive vaccine.” How wonderful would it be to have a vaccine that could avoid the next pandemic when developing a variant-proof Covid vaccine?