Everything you need to know about next-generation coronavirus vaccines
COVID-19 vaccines helped many of us to return to our normal lives, but coronavirus vaccines providing broader or longer-lasting protection are on the horizon.
- 25 March 2025
- 6 min read
- by Linda Geddes
COVID-19 vaccines changed the course of the pandemic, enabling most of us to return to our everyday lives.
But while these vaccines are highly effective against severe disease, they’re not perfect. Current vaccines don’t provide complete protection against getting infected or infecting others, and people require regular boosters to maintain that level of protection.
They also don’t protect against other coronaviruses, such as the virus that causes Middle East respiratory syndrome (MERS), seasonal coronaviruses that cause common colds or future coronaviruses with pandemic potential.
We could do better
SARS-CoV-2 is just one member of a vast family of coronaviruses with multiple hosts, whose genomes are highly susceptible to mutation – meaning they have the potential to jump to humans.
“The threat of coronavirus spillovers is expected to continue and may even intensify in coming years, given rapid changes in climate, human and wildlife activity,” says Dr Nadia Cohen, Research & Development Programme Lead at the Coalition for Epidemic Preparedness Innovations (CEPI).
“It is crucial that the world continues to invest in coronavirus R&D to help humanity stay one step ahead.”
The good news is that next-generation coronavirus vaccines are being developed that could provide broader, stronger and longer-lasting protection.
The technologies underpinning them could also be deployed against other pathogens, strengthening our defences against existing and future disease threats.
Here’s everything you need to know about the innovations underpinning these vaccine candidates.
Mucosal vaccines
Whereas most vaccines are designed to stimulate immune cells that circulate in the blood, the goal of mucosal vaccines is to target immune cells in mucosal tissues, such as the lining of the nose, mouth, lungs or intestines.
For respiratory viruses, such as coronaviruses, mucosal surfaces are their first port of entry into our bodies, making immune cells stationed there are our first line of defence. Targeting these cells through vaccination could result in stronger protection against infection.
“This could mean that if I’ve been vaccinated, I might not produce as much infectious virus for as long, so I’m less likely to infect other people, helping to breaking chains of transmission,” says Prof John Tregoning, Professor of Vaccine Immunology at Imperial College London, UK.
However, conventional injected vaccines aren’t very good at triggering mucosal immunity, so researchers are exploring alternatives – including inhaled, nasal and oral vaccines.
“There is huge promise in the approach,” says Prof Christopher Chiu at Imperial College London, who is leading a CEPI-funded project to develop advanced, transmission-blocking coronavirus vaccines, including mucosal vaccines.
“Historically, we haven't known enough about what goes on in the nose and lung during an infection, compared to the blood, but we now recognise that – while not entirely separate – they are different.”
"We have a real opportunity to identify the types of vaccines and technologies that could target it to reduce or block transmission and have these on standby for the next pandemic, when we could switch the appropriate antigens in.”
Nasal vaccines are already used to help protect children against seasonal influenza in many countries, and several intranasal COVID-19 vaccines are currently in late-stage clinical trials.
Most of these COVID-19 vaccine candidates use a harmless, modified virus – known as a vector virus – to deliver virus antigens into the body, but at least one company, Codagenix, is testing a live attenuated nasal vaccine, which uses a weakened version of SARS-CoV-2 to trigger a mucosal response.
Broadly protective vaccines
Given the size and diversity of the coronavirus family, developing a single ‘pan-coronavirus’ vaccine that can protect us against all of them is unlikely, says Cohen.
However, vaccines that trigger immunity against specific subgroups are more feasible.
Most advanced are candidates against sarbecoviruses – a subgroup that includes SARS-CoV-2, the virus that cause SARS, and various bat coronaviruses.
“Though many questions remain along the road to creating a successful human vaccine, pre-clinical data so far have been promising and suggest that generating a broadly protective sarbecovirus vaccine is technically feasible,” says Cohen.
“The timeframe for development of a human vaccine may depend on the end goal of development. Nevertheless, we expect a number of candidates to initiate clinical testing in the coming year or two.”
Vaccines against the broader sub-family of coronaviruses known as betacoronaviruses, might also be feasible. These vaccines would not only protect against SARS-CoV-2, but MERS, as well as the four known seasonal coronaviruses that cause cold-like symptoms in humans.
T cell vaccines
One approach to developing broadly protective vaccines is to focus on viral proteins that are common within and between coronaviruses.
For instance, although SARS-CoV-2 frequently alters its surface ‘spike’ protein to avoid our immune systems, the proteins it uses to replicate appear less susceptible to change. They also seem to be broadly similar across different coronaviruses.
By testing which parts of these proteins trigger the strongest and most broadly protective responses in immune cells, Dr Leo Swadling at University College London, and colleagues hope to identify antigens that could be incorporated into broadly protective vaccines.
As well as triggering antibodies, the hope is that this approach would be better at stimulating T cells – immune cells that recognise and destroy virus-infected cells – resulting in broader, longer-lasting protection.
“Vaccine-induced T cells tend to be more durable than antibodies. But although you get some induction of T cells with existing vaccines, they are not specifically designed to maximise this part of the immune response,” says Swadling.
Mosaic vaccines
Another approach is engineering spike proteins to incorporate molecular features from other coronaviruses, or linking multiple spike proteins or spike regions together.
“Building on advances in material science, we can now include multiple versions of the same protein – for example, show the immune system spike from MERS, SARS-CoV-2 and SARS-CoV-1 at the same time, hopefully inducing immunity to all three,” says Swadling.
Even though coronaviruses frequently alter their spike protein to evade immune detection, some regions that bind to our cells and enable the virus to gain entry tend to remain unchanged across many different coronaviruses.
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Targeting immune responses at these regions could make it much more difficult for viruses to evolve to escape vaccine-induced antibodies.
A vaccine candidate known as Mosaic-8 attaches up to eight different versions of these protein fragments to nanoparticles. Studies in mice and non-human primates have suggested that the vaccine not only triggered protective immune responses against the viruses contained within the vaccine, but against some other beta coronaviruses as well.
Promising as such approaches are, “to be translated to human vaccines, they will need to overcome important manufacturing issues linked to the complexity of their designs, as well as regulatory hurdles,” says Cohen. “Nevertheless, in animal models, several of these efforts have shown the ability to elicit immune responses against both viruses that are represented in the vaccines, but also, critically, against related viruses that are not.”
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