Could a nasal vaccine finally banish Covid?

The emergence of a new, ‘highly infectious’ Covid variant — responsible for more than 40 per cent of cases in the U.S., where hospitalisations reached more than 40,000 a day in December — is a grim reminder that the pandemic is far from over.

This comes as concerns rise about the effects of China’s reversal of its zero-Covid approach, leaving its huge population, who have little natural immunity to the virus, able to resume normal life and travel.

Even here, despite most of the population having booster after booster, there are around 9,000 people in hospital with Covid in England alone. That’s up from 4,900 at the beginning of December, according to NHS data.

So will we ever truly wave goodbye to this pandemic?

Locked away in a laboratory in Bangladesh is a box of white powder developed by scientists at Lancaster University that may prove a key weapon in helping us do just that.

That’s because this powder, when mixed with saline, can be used as a vaccine against Covid-19. But unlike current Covid vaccines, it’s not injected into your arm: it’s squirted up your nose.

Crucially, whereas other vaccines reduce the risk of serious disease and death, the hope is that this one, called ViraVac, will be more successful at cutting the risk of becoming infected in the first place. It could represent a sea change in the approach to vaccination against Covid — and potentially other respiratory viruses, too.

ViraVac is based on a vaccine sprayed around barns to halt a form of coronavirus in chickens. It is one of around a dozen nasal Covid vaccines being developed.

One of these includes a two-dose nasal vaccine now being produced in India that was developed by Washington University in the U.S. and has been approved in India as a primary vaccine and as a booster. The vaccine was given emergency approval after studies showed that it gave ‘complete protection’ against certain strains of Covid, after six weeks.

Elsewhere around the world, scientists have been trying to perfect their own nasal vaccines — because the more we learn about the virus, the more some believe that targeting the immune system this way is the best chance of halting the march of Covid for good.

With the standard injection, the protection varies according to the vaccine and the variant it is up against. For instance, the Moderna booster offered an impressive 90 to 95 per cent protection against hospitalisation with a Covid-19 infection nine weeks after vaccination, according to UK Health Security Agency data released last January. But the protection drops when it comes to catching Covid — while it offers 63 per cent protection against the BA.1 Omicron variant and 70 per cent against the BA.2 after two weeks, after 25 weeks that falls to 9 per cent protection against BA.1 and 13 per cent against BA.2.

‘One of the failures of current vaccines is that they don’t provide long-term protection — we rely on multiple boosters — and they don’t prevent the virus being transmitted or block infection,’ says Lawrence Young, a professor of virology at Warwick University.

Muhammad Munir, a professor in virology and viral zoonoses at Lancaster University, believes nasal vaccines offer a solution as they ‘halt community transmission’ — in other words, stop people getting ill with Covid and passing it on.

‘It offers the chance to get a full handle on this pandemic,’ he says.Central to this is the fact that nasal vaccines work on different parts of the immune system compared with vaccines given intramuscularly (i.e. as an injection typically given into the arm).

Professor Munir says that’s because Covid enters the body via infected droplets that gain entry mainly through the nose or mouth, the logical approach is to focus the immunological fight there. As he explains, vaccines given into the arm produce T-cells (which knock out infected cells) and B-cells (which produce antibodies that attack invading pathogens).

‘But these immune cells are predominantly in the bloodstream and organs, with only a tiny quantity in the nose and mouth so they aren’t guarding the point of entry.

‘And yet for Covid the route of transmission is through the nose and mouth. This area is lined by a mucus membrane that continues to the gut and is enriched with an armoury of immune cells.

‘If a vaccine is inhaled or given as drops through the nose or mouth then it will prime these cells, which are the first line of defence, to act quickly.’

T-cells and B-cells in the mucosal layer can prompt a lightning-fast attack ‘pretty much the instant the virus comes in’, attacking it before it has a chance to infect cells, he says. ‘These nasal immune cells get to work in a couple of minutes — whereas the immune cells made by intramuscular vaccines get to work six to eight hours after entry of the virus.’

This time difference, he says, is vital. ‘If just one virus particle successfully sticks to one cell it takes over that cell and replicates to produce a million more viruses in an eight-hour cycle,’ says Professor Munir, who has been leading the research into Lancaster University’s nasal vaccine.

‘That’s why the nasal vaccine will have the advantage — the immune cells it produces in the nasopharyngeal region can act immediately. It’s a bit like having the police sitting and waiting for a crime to be committed.

‘With the intramuscular vaccine approach, the police only come once the problem is there, and by that time damage could be done.’

Certainly, animal studies of his nasal vaccine look promising.

A study published in the journal iScience in August 2021 found that hamsters given it had ‘complete protection’ from lung infection and inflammation — and did not shed viral particles when infected with Covid, which suggested that it would stop onward infection.

Reducing transmission is an attractive proposition, not just to reduce cases but also because it may prevent long Covid.

Continued high transmission also leaves the door open to more variants of the virus — currently, for example, the new XBB.1.5 variant is already responsible for one in 25 cases in the UK. ‘The fact that we haven’t halted transmission is why we are on our tenth variant of concern,’ says Professor Munir. ‘The emergence of this newly identified Omicron variant — which is worrying because we don’t know yet how protective current vaccines will be — shows the importance of this, and there could be more around the corner.’

It’s not just Covid: there is a buzz in the scientific community about nasal vaccines for respiratory infections and the mucosal immunity they offer, says Professor Peter Openshaw, an immunologist at Imperial College London.

‘I was at a [vaccine] conference recently where one in four presentations was arguing the importance of mucosal immunity and not systemic [i.e. body-wide] — and that’s a big change.’

If you can stimulate a good immune response in the mucosal layer, the immune cells in the nose can then travel around the rest of the mucosal layer down to the gut lining, adds Professor Young.

He says that this defence in the mucosal membrane in the gut against Covid especially may have unexpected benefits: ‘A proportion of people with long Covid have gut symptoms. And data suggests the virus can persist in the gut, so providing greater protection at the mucosal layer in the gut may help with that, too.’

A nasal vaccine would also clearly be good news for needle-phobics — a 2021 study by Oxford University, which questioned 15,000 people, suggested 10 per cent of all vaccine hesitancy was linked to needle phobia, reported the journal Psychological Medicine.

‘When the news was released [in 2021] that we were working on a nasal vaccine for Covid, we started getting emails from people all over the country asking if they could try it as they don’t like needles,’ says Professor Munir. However, there are drawbacks to nasal vaccines. ‘The one big advantage of injectables is you know exactly how much is being administered,’ says Professor Openshaw. With nasal vaccines you can’t be so sure if some of it is sneezed out or swallowed.’

A nasal flu vaccine, called Fluenz Tetra, is already being offered to children aged two and three or those with underlying health conditions aged two to 17. It contains a live but weakened form of the flu virus. But attempts to develop nasal vaccines that are not based on weakened viruses for other respiratory infections have not yet been successful — a key problem being how to keep the inhaled vaccine in place long enough.

‘The nose is lined with mucus and hair-like cells, which are good at binding to stuff and carrying it backwards into the stomach — potentially rendering a nasal vaccine useless,’ says Professor Openshaw.

There are other hurdles for nasal vaccines for Covid. Michael Diamond, a professor of medicine at Washington University, who helped develop the nasal vaccine that has been passed for use in India, says governments preferred to fund the development of intramuscular vaccines over others.

‘We have a 50-year or more history of giving vaccines via the intramuscular route — we don’t have that track record with these [nasal] vaccines,’ he told Good Health.

‘The U.S. government gave a lot of support to companies to work with vaccines that they thought were more likely to succeed. That consumed a lot of resources so there was not much left to support new initiatives.’

After Washington University developed the nasal vaccine, a company in India (Bharat Biotech) licensed its technology and developed it.

Funding was thin on the ground in the UK, too, says Professor Munir. ‘There were three or four vaccine options [not nasal] on the table early on and funding for anything else dried up,’ he says.

And in his case there was also a personal reason to delay work. When the pandemic broke, his young son, Ibrahim, was gravely ill in hospital with a genetic disease. With 12 years’ experience working with coronaviruses, his opinion was keenly sought and he spent much time talking to other virologists while in hospital corridors — but was in no position to get into the lab. Ibrahim died aged five in February 2020 and it wasn’t until August 2020 that Professor Munir felt able to get back to work.

‘My motivation was if I can’t do anything to save my son, perhaps I can do something to save humanity,’ he says.

He and his small team set to work modifying the vaccine he originally developed for the poultry market.

‘Coronaviruses wipe out the poultry industry in countries such as Egypt and Pakistan,’ he says. ‘How we deal with these is to give them a nasal vaccine [sprayed into the air]. All coronaviruses are spread through droplets and this is the best way to stop transmission.’

The vaccine is a type of viral vector vaccine. It uses a harmless virus such as a cold virus but within it is a piece of the genetic code of the Covid spike protein, which helps imitate an infection.

But whereas the one used in the Oxford/AstraZeneca vaccine was a virus that caused cold-like symptoms in chimps, this one contains a virus that affects poultry.

‘And it has a receptor that sticks to the nasal tract — it’s designed to develop a respiratory infection which makes it perfect to deliver a nasal vaccine,’ explains Professor Munir.

Modifying the original vaccine — which would be given to humans as two doses, one month apart — to be specific to Covid meant they had to ensure the portion of the spike protein they put into the virus carrier stayed put.

‘We were working until 2am most days for weeks on end,’ he says. He recalls the ‘whoop whoop feeling’ when the team realised the vaccine was stable even at -4c (25f) to 37c (99f) — meaning it wouldn’t need expensive storage facilities, unlike the Pfizer vaccine.

‘Then came the frightening part of trying it in animal studies,’ he says.

But, as the research with hamsters showed, it was highly effective. The vaccine is now being refined ahead of human trials due to start this year on 30,000 volunteers in Bangladesh and Peru (where they have high infection and low vaccination rates).

If successful, it could be used to vaccinate large numbers of people cheaply and quickly.

And ‘the know-how could then be piggy-backed to develop nasal vaccines for other contexts — even for things such as cancer’, says Professor Young.

The road forward may have its twists and turns, however. Questions remain, for instance, over the length of immunity that nasal vaccines offer.

‘If the lining of your nose remembered every single thing it has ever responded to, it would become overloaded, so your immunological memory there is usually of quite limited duration — which may be a necessary adaptation,’ says Professor Openshaw. ‘This kind of immunity then tends to be short-lived.’

Professor Munir says: ‘We won’t know how long the immunity it gives lasts until it starts going up people’s noses. But I believe this is going to work well.’

Professor Young adds: ‘News of this latest variant is a wake-up call that we aren’t quite out of the woods yet with Covid — and a nasal vaccine might be the answer we need now.’

What’s behind the hacking cough that’s making everyone feel so rotten? ANGELA EPSTEIN reveals the reasons behind the tide of illness

From Covid to flu and the nasty cold doing the rounds, it seems most people are currently battling a bug.

So much so that pharmacies have been selling out of cold and flu remedies such as Lemsip.

Multiple factors are behind this tide of illness, says Neil Mabbott, a professor of immunopathology at Edinburgh University.

‘In recent winters there was limited mixing indoors, as well as widespread use of face coverings and social distancing. We’re now mixing indoors and using public transport much more, and in larger groups, providing greater opportunities for these common infectious diseases to spread.’

The situation is being exacerbated by the fact that this winter there appears to be a particularly virulent cold in circulation, says Danny Altmann, a professor of immunology at Imperial College London.

‘The current one seems highly infectious and brings a really lasting hacking cough,’ he told Good Health.

John Oxford, an emeritus professor of virology at Queen Mary, University of London, concurs.

‘It has been an extraordinary winter so far,’ he says. ‘There seems to be a lot of infection going around. There are also dozens of varieties of cold virus and we can get reinfected with each one.’

And then there is the so-called ‘immunity gap’, adds Professor Paul Hunter, an expert in infectious diseases at Norwich Medical School. This is the result of lockdowns reducing our usual exposure to seasonal viruses, so we have little natural immunity to them now that they’re back in circulation. And the longer it is since previous exposure, the greater our chance of catching an infection.

‘So if someone was exposed to flu three months after their original bout, then they’ll probably not develop the illness again,’ says Professor Hunter.

‘If exposure happens a year later, it might lead to a standard bout of flu — unpleasant but not dangerous as they won’t have high levels of antibodies to it, but they’ll have at least some.

‘But there’s now a three-year gap between previous and current exposure to flu, and this can lead to a severe form of it.’ The same may apply to other respiratory infections.

How long we succumb to a virus — and how long it takes to feel normal — depends on factors such as the infection, your vaccination status, previous infections as well as your age. But is there anything we can do to speed up recovery?

Most medication fights symptoms rather than the cause, so they won’t speed up recovery, says Professor Hunter. Prescription anti-viral drugs can do this, but are usually only offered for severe flu in vulnerable people.

‘For most people, by the time you know it’s flu, it’s too late to take them and they do little to help,’ says Professor Hunter. (Studies show antiviral drugs work best when started within two days of getting sick.)

A more accessible form of treatment is sleep. A 2019 study in the Journal of Experimental Medicine found that a good night’s sleep can increase the function of T-cells — white blood cells that kill invading bacteria and viruses.

‘Our body’s circadian rhythms [24-hour cycle] and nocturnal sleep play important roles in regulating our immune system,’ explains Professor Mabbott.

‘That’s why disturbed sleep can reduce the effectiveness of our immune responses, either to infections or vaccines.’

Dr Steven Kinnear, a Bangor-based GP in County Down, says: ‘Since sleep is vital to gee up recovery, I use the children’s remedy Calpol Vapour Plug & Nightlight, which can stop a blocked nose disturbing my rest.’ (The vapours help decongest, he says.)

Eating well helps, too. ‘Think Mediterranean diet, rich in colourful plants, each with their own host of anti-inflammatory and antioxidant nutrients,’ says Dr Jenna Macciochi, a senior lecturer in immunology at Sussex University and author of Your Blueprint For Strong Immunity.

‘Focus on protein, too, as this provides the building blocks for the different components of our immune system. In addition, your tissues may have incurred damage from the infection — protein is important to rebuild and repair.’

She suggests omega-3 supplements, as these fats are the raw materials for our immune system anti-inflammatory mechanisms (to turn off inflammation and help repair and recovery).

The reason we’re advised to drink plenty of fluid is partly to help thin mucus, so it drains away more easily, relieving congestion, says Dr Kinnear.

‘But limit alcohol,’ adds Dr Roger Henderson, a GP in Shropshire. ‘Too much can lead to vitamin deficiencies, which can affect your immune system.’

And pace yourself when it comes to exercise. ‘Pushing yourself before you’re ready can set you back, and make you even more exhausted,’ says Dr Gavin Francis, a GP and author of Recovery: The Lost Art Of Convalescence. ‘It’s important knowing that it’s OK to rest a bit — and that it might take a good few weeks to improve.’

Convalescing is a vital part of recovery, agrees Dr Macciochi. ‘In today’s fast-paced world, we feel we have no time to be ill — we’re all looking for a quick fix and then to get back to our normal daily life quickly,’ she says. ‘Recovery takes time. Health doesn’t begin when acute symptoms end.’