Over a year after the United States approved its first vaccines, COVID cases continue to pile up, leaving many vaccinated people wondering, “Do I need a vaccine upgrade?” People who are fully vaccinated and boosted have been tested positive in large numbers, especially since the omicron-triggered wave started its relentless burning across the United States in December. Vaccines that once led experts to declare COVID-19 a “pandemic of the unvaccinated” not protect as well against disease, although they continued to protect against the most serious disease. Breakthrough infections are so common that the almost miraculous protection that the vaccine promised a year ago feels very far away.
Part of the problem is that the virus that the vaccines are targeting – 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 against the virus that is spreading now, and finding a way to protect humans from future variations of the virus.
On June 28, an FDA committee will meet to discuss whether and how future booster doses of vaccines can specifically target new variants of the virus. Like the seasonal flu shot, the next few vaccines can at some point protect against the version of the virus that is going to circulate in a given year. At the same time, other researchers are investigating ways to make the protection against any booster shot last longer. In the long run, COVID-19 vaccines can be very different from current shots, using other technology and protecting against viruses that do not even exist yet. Some may not be shots, but nasal sprays, which may prevent even mild infections.
“Preventing serious illness was the original goal, and I understand that. At the beginning of the pandemic, it made sense, ”he said Akiko Iwasaki, professor of immunobiology at Yale University School of Medicine. “But now we understand the virus better and the fact that the variants are here – I think we need to change our thinking.”
The next virus
The first step for the future of COVID-19 vaccines is to catch up with the recent past. After over two years, it has the version of the virus that was first discovered in Wuhan, China has been replaced by its more infectious and immunosuppressive variants. Several vaccine manufacturers have already started testing vaccines tailored to the omicron variant. An early analysis of Modern’s omicron-specific shots showed that 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 taste” coronavirus and omicron.
Moderna says its booster may be “available in late summer in some markets,” Elise Meyer, senior director of communications at Moderna, wrote in an email to The edge.
Pfizer and BioNTech are also running one clinical trials to update their shots against omicron, examine standard booster shots of the original vaccine, a version aimed only at omicron, and a bivalent shot like Modernas. At a press briefing in April, Pfizer CEO Albert Bourla said an omicron shot may be available in the fall.
Novavax, whose vaccine can be approved soon in the US, working on its own omicron booster. Dens clinical trials testing of both the omicron-targeted shot and a bivalent vaccine began on 31 May. The vaccine, which has been under review by the FDA since January, seems to have less serious side effects than the other vaccines, making it potentially ideal to use as a non-disruptive booster.
But it is still unclear whether the omicron shots will work much better than the original vaccine against omicron and other variants. In a study on mice, the original vaccine “actually worked quite well, at least in the short term,” he said. Larissa Thackrayan associate professor of infectious diseases at the Washington University School of Medicine in St. Louis; Louis.
If omicron-specific vaccines do not have a major advantage over existing vaccines, it may be difficult to sell them for FDA approval. Despite the uncertainty, Thackray said she believes an omicron booster is required. A vaccine targeting a current or at least newer variant makes more sense than a vaccine targeting a very different virus – the original strain of SARS-CoV-2, which no longer exists.
At some point, the omicron may no longer be circulating either. It has already evolved into several sub-tribes, and the virus will only continue to evolve. Finding a way to keep the images up to date is a way to keep track. But other researchers are working on “universal” vaccines – which could theoretically protect against any new form of the virus.
Vaccines like this benefit from the immune system’s ability to respond to the parts of viruses that remain the same as they develop, said David Martinezan immunologist at the University of North Carolina at Chapel Hill and an author of one 2021 survey investigating a proposed universal coronavirus vaccine.
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 to current and future variants, as well as other coronaviruses that could cause another pandemic. It is still preliminary – the special universal vaccine has only been tested on animals – but it is a first step towards broad protection.
This type of vaccine can still work even if the virus changes significantly, Martinez said. But it will be a long time before we know if this is true – it is likely that this kind of vaccine will take years for researchers to develop, test and be approved, he said.
Universal vaccines are not the only next generation products in development. Researchers are also working on vaccines that are not shots at all – they are nasal sprays.
Intranasal vaccines could protect against the virus right where it enters the body, he said Iwasakithe immunobiologist at Yale University School of Medicine.
“It makes sense to establish immune systems right at these mucous membranes,” she said, referring to the inside of the nose. “It can prevent infection of these tissues completely.” Without infection, people would not transmit the virus and they would be protected from prolonged COVID.
An intranasal vaccine has been given now – FluMist – but it uses a weak version of the live flu virus, which is not safe for immunocompromised people. Iwasaki and her colleagues are working on a strategy to work around this problem: Using a nasal spray containing a version of the COVID-19 virus’ nail protein as a booster after an initial mRNA shot. 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 first shot 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 helped found a company, Xanadu Bio, to make these vaccines, even though she says they are still raising money to start clinical trials and working on testing the vaccine in non-human primates. And Xanadu is far from the only one looking at nasal spray vaccines. There are already more than a dozen clinical trials of intranasal vaccines underway in the United States and globally.
There are still many challenges ahead before the next set of COVID-19 vaccines is available to the public. There is still a lot, experts do not know about the current vaccines – as why they lose their effectiveness over time, regardless of new variants, says Deepta Bhattacharya, professor of immunobiology at the University of Arizona College of Medicine. He says that it can be difficult to know exactly what it is about a vaccine 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 it’s almost as much guesswork as it is science to try to extract which of these differences are really important.”
There are also practical limitations. The FDA meeting next week to discuss vaccination against COVID-19 variants could have a major impact on the direction future vaccine development will take. Funding, both for new research and for making footage available to people for free, is also likely to be an issue. Unless Congress can agree on more pandemic funding, free future vaccines could be limited only to the most vulnerable people.
After all, Bhattacharya is optimistic about the future of COVID-19 vaccines. Research seems to show that the combination and refinement of next-generation vaccine techniques such as intranasal, vaccine-targeted and universal vaccines could be very successful, he said.
“I think science is definitely there to get better vaccines in the coming years,” he said.