Where’s the next generation of COVID-19 shots?

Over a year after the United States authorized its first vaccines, COVID cases continue to pile up, leaving many vaccinated people wondering, “Do I need a vaccine update?” People who have been fully vaccinated and boosted have tested positive in huge numbers, particularly since the wave triggered by omicrons began burning incessantly in the United States in December. The vaccines that once led experts to declare COVID-19 an “unvaccinated pandemic” don’t protect as well against disease, even though they have continued to protect against more serious diseases. Breakthrough infections are so common that the near miracle protection promised by the vaccine a year ago seems a long way off.

Part of the problem is that the virus that vaccines target, the first version of the coronavirus that started spreading in early 2020, no longer exists. Now, regulators, researchers and vaccine companies are turning to the next stage of the vaccine development process: finding a way to protect themselves from the virus that is spreading now and finding a way to protect people from future variations. of the virus.

On June 28, an FDA committee will meet to discuss whether and how future booster doses of vaccines could specifically target emerging variants of the virus. Like the seasonal flu vaccine, upcoming vaccines could at some point protect against whatever version of the virus circulates in a given year. At the same time, other scientists are looking for ways to make protection from any booster shot last longer. In the long run, COVID-19 vaccines could be very different from current vaccinations, using different technologies and protecting against viruses that don’t yet exist. Some may not be injections but nasal sprays, which may be able to prevent even mild infections.

“Preventing serious illness was the original goal, and I understand that. At the start of the pandemic, it made sense,” said Akiko Iwasaki, a professor of immunobiology at Yale University School of Medicine. “But now we understand better the virus and the fact that the variants are here, I think we need to change our mind.”

The next virus

The first step towards the future of COVID-19 vaccines is to play with the recent past. After more than two years, the version of the virus that was first detected in Wuhan, China, has been replaced by its more contagious and immune variants. Several vaccine manufacturers have already started testing vaccines tailored to the omcron variant. An initial analysis of Moderna’s omicron-specific injection showed it generated more antibodies to the omicron virus than the original vaccine, the company announced earlier this month. The vaccine is bivalent: it is made to protect against both the “original flavor” coronavirus and omicron.

Moderna says its booster may be “available by the end of the summer in some markets,” wrote Elise Meyer, Moderna’s senior communications director, in an email to The border.

Pfizer and BioNTech are also conducting a clinical trial to update their shots against omicron, looking at the standard booster shots of the original vaccine, a version aimed only at the omicron, and a bivalent shot like that of Moderna. At a press conference in April, Pfizer CEO Albert Bourla said an omcron shot may be available in the fall.

Novavax, whose vaccine may soon be approved in the United States, is working on its own omicron booster. On May 31, the clinical trial began that tested both the omicron targeted injection and a bivalent vaccine. The vaccine, which has been under FDA review since January, appears to have less severe side effects than other vaccines, making it potentially ideal to use as a non-disruptive booster.

But it’s still unclear whether omicron shots will work much better than the original vaccine against omicron and other variants. In one study in mice, the original vaccine “actually worked quite well, at least in the short term,” said Larissa Thackray, an associate professor of infectious diseases at Washington University School of Medicine in St. Louis.

If omicron-specific vaccines do not have a major advantage over existing vaccines, they may be difficult to sell to be licensed by the FDA. Yet despite the uncertainty, Thackray said he thinks an omicron booster is overdue. A vaccine that targets a current or at least recent variant makes more sense than one that targets a very different virus: the original strain of SARS-CoV-2, which no longer exists.

At some point, even the omcron may no longer circulate. It has already evolved in several sublines and the virus will continue to evolve. Finding a way to continually update your shots is a way to keep up. But other researchers are working on “universal” vaccines, which could theoretically protect against any new form of the virus.

Vaccines like this one harness the immune system’s ability to respond to parts of viruses that remain the same as they evolve, said David Martinez, an immunologist at the University of North Carolina at Chapel Hill and author of a 2021 study examining a universal coronavirus vaccine proposal.

Martinez and other researchers made their vaccine by combining genetic material from a handful of different coronaviruses. Their goal was to make a shot that could generate an immune response against current and future variants as well as other coronaviruses that could cause another pandemic. It’s still preliminary – that particular universal vaccine has only been tested on animals – but it’s a first step towards broad protection.

This type of vaccine may still work even if the virus changes substantially, Martinez said. But it will take a long time to know if this is true – this type of vaccine is likely to take years for scientists to develop, test and get approval, he said.

Shots without shots

Universal vaccines aren’t the only next-generation products in development. Researchers are also working on vaccines that aren’t injections at all – they’re nasal sprays.

Intranasal vaccines could protect against the virus right where it enters the body, said Iwasaki, an immunobiologist at Yale University School of Medicine.

“It makes sense to establish an immune defense at precisely these mucosal sites,” he said, referring to inside the nose. “It can completely prevent infection of these tissues.” Without infection, people would not transmit the virus and would be COVID protected for a long time.

There is an intranasal vaccine being administered now – FluMist – but it uses a weak version of the live flu virus, which is not safe for immunocompromised people. Iwasaki and his colleagues are working on a strategy to get around this: use a nasal spray containing a version of the COVID-19 virus spike protein as a booster after an initial mRNA injection. Because it is used as a booster, the spray does not need to contain a live virus to trigger a strong enough immune response – immunity from the initial injection is enough to drive a strong response to the protein in the spray.

So far, the technique is experimental and has only been tested on mice. But Iwasaki co-founded a company, Xanadu Bio, to make these vaccines, though he says they are still raising funds to start clinical trials and work to test the vaccine on non-human primates. And Xanadu is far from the only one looking at nasal spray vaccines. There are more than a dozen clinical trials of intranasal vaccines already underway in the United States and around the world.

There are still many challenges ahead before the next round of COVID-19 vaccines is available to the public. There are still many experts who don’t know about current vaccines, for example because they lose their effectiveness over time, regardless of new variants, says Deepta Bhattacharya, a professor of immunobiology at the University of Arizona College of Medicine. He says it can be difficult to know exactly what a vaccine is that makes it work well for a long time.

“When you compare one vaccine to another, there are a lot of things that are different,” he said. “And so trying to extract which of these differences are really important is almost as much conjecture as science.”

There are also practical limitations. The FDA meeting next week to discuss vaccination against COVID-19 variants could have a big impact on the direction that future vaccine development will take. Funding, both for new research and for making the photos available for free to people, is likely to be an issue as well. Unless Congress can agree on more funding for the pandemic, future free vaccines could be limited to only the most vulnerable people.

Despite everything, Bhattacharya is optimistic about the future of COVID-19 vaccines. Research appears to show that combining and refining next-generation vaccination techniques such as intranasal, vaccine-targeted, and universal vaccines could be highly successful, he said.

“I think the science is definitely there to have better vaccines in the next few years,” he said.

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