New types of COVID vaccines are being tested. Here’s where we stand

Forget rolling up your sleeve.

If Matthew Miller and his team have their way, you could one day go to get a COVID-19 vaccine and spend about a minute of your day inhaling a tasteless, odourless mist. It would swoosh down the airway and into your lungs — sparking an immune response that would, in theory, stop the virus right where it can hit your body the hardest.

“When we give a vaccine in the arm, those cells don’t know to live in the lung,” Miller says.

“What we’re doing, basically, when we vaccinate someone in the arm is really diluting the immune response throughout our whole body,” he adds. “What we would like to do is really focus the strongest part of the immune response at the site where infection occurs.

Miller and his colleagues at McMaster University in Hamilton are currently in the first phase of human trials with their inhalable shot. Assuming all goes smoothly, they hope to have completed testing by the end of next year.

If you think that makes them late to the fight against this pandemic, think again.

Almost two years after COVID vaccines began shipping out across the world, the search for more vaccines is not over, as candidates chug their way through human testing.

But the goalposts for success have moved. Whereas researchers once pursued a shot, any shot, that was safe and at least 50 per cent effective in the hopes of slowing the spread of a virus that had overwhelmed much of the world, the needs of the pandemic fight have evolved.

Health officials in several provinces, including Ontario, are opening another round of booster doses, in part because the new, super-spreadable BA.5 variant is better than ever at evading previous protections.

The vaccination campaign may be moving into a new phase, in which protection will have to be boosted occasionally, which doesn’t mean the vaccines aren’t working.

“Think about the flu vaccine. We don’t ever talk about being fully vaccinated against flu,” notes Alan Bernstein, president and CEO of the research organization CIFAR and a member of Canada’s COVID vaccine task force.

The current crop of vaccines remains good at preventing serious disease, but their protection against the spread of the virus is faltering. Meanwhile, most doses are manufactured by the wealthy world and remain out of reach of our poorer neighbours. Some are just too expensive.

In particular, shots updated to target new variants will be critical, says Dr. Sharmila Shetty, a vaccines medical adviser for Médecins Sans Frontières.

“We need to be thinking of second-generation vaccines, not just more of the same,” she says.

Here are some of the new vaccines that could eventually be rolling out.

Inhalable vaccines

Doing away with syringes would be a win for the needle-phobic, but inhalable vaccines could also, some researchers hope, mean giving the lungs supercharged protection.

When you get a vaccine the conventional way, it prompts an immune response involving antibodies and T cells in your blood, which are then distributed throughout your body, says Miller.

While that’s generally useful in fighting off pathological invaders, COVID targets the respiratory tract — so researchers wondered if the vaccine could do that, too.

“What we would like to do is really focus the strongest part of the immune response at the site where infection occurs,” he says.

It is a relatively new way of doing things for the simple reason that you can’t inhale most traditional vaccines — they would get stopped by the moist linings of your lungs and intestinal tract.

Taking the vaccine would be like inhaling a mist, Miller says. The drops of a nasal spray are too big to be deposited in the lungs, where protection is most needed, so the team made it fully inhalable, like using a puffer or a nebulizer. But it’s tasteless and odourless, he says, and would require you to just breathe.

However, researchers are now using modified versions of other pathogens that infect your lungs to carry in bits of new virus like the coronavirus, that aren’t able to infect you. It’s essentially how the relatively new inhalable flu vaccine known as FluMist works.

Now, researchers involved with dozens of vaccine candidates around the world are looking at some version of this type of vaccine delivery.

The hope is that these types of vaccines would be better at preventing infection, not just serious disease. This method also requires less of the active part of the vaccine, meaning it might spark fewer side effects, adds Miller, who is co-heading the development of an inhalable vaccine at McMaster.

Vaccines tailored to the variants

Moderna has become the first vaccine maker to seek authorization for a new vaccine in Canada targeted at the Omicron variant of COVID. Health Canada is now reviewing the U.S. drugmaker’s new booster shot that includes the company’s original formula, plus one updated to target new strains.

In a release posted to its site on June 22, Moderna CEO Stéphane Bancel said the company planned to submit the new data to regulators “urgently” and was preparing to roll out shots by August, ahead of a potential fall rise in cases.

Variants BA.4 and BA.5 in particular represent “an emergent threat to global public health,” the statement said. As of Canada Day the new variant BA.5 was expected to make up 70 per cent of cases in the country. While the new subvariants of Omicron are considered to be no more severe than previous strains, experts say they do appear more spreadable and more able to evade the protection granted by previous vaccines and infections.

The updated versions of the COVID vaccines won’t have to undergo the same large-scale testing that early shots did because their safety has already been determined, a Health Canada spokesperson said in an email. Instead, small-scale studies will be done to prove the updated versions are effective against new strains.

This is a similar process to how flu vaccines are authorized every year — although the shots are updated to fight new flu strains, the basic vaccine technology remains the same.

The original purchase agreements that Canada signed to buy vaccine doses “provide sufficient flexibility” to get new versions of the vaccine once they are authorized, the spokesperson says.

A universal COVID vaccine

One of the biggest challenges facing vaccines going forward is that the virus has proven able to morph and evade some of the prior protections granted by the shots.

But what if a vaccine knew how to target all coronaviruses and not just the variant of the month? That, in many ways, is the current Holy Grail of vaccine development, as new funding reflects.

According to Nature, the Coalition for Epidemic Preparedness Innovations, a global organization that works to develop vaccines, has poured $200 million (U.S.) into the research and development effort, while the U.S. National Institute of Allergy and Infectious Diseases has earmarked $43 million.

“These pan-variant vaccines or variant-proof vaccines, I think, are going to be really important for the future,” Shetty says.

When you imagine a single coronavirus, you probably picture a floating orb covered in spikes.

Most of the first wave of vaccine makers designed their shots to teach your immune system to recognize those spikes, in particular. Not only are they distinctive, but they act as little arms to allow the virus to grab onto your cells and infect you.

However, because your immune system is primed to notice those spikes in particular, mutated versions of the virus that have different-looking spikes tend to have an advantage, and new variants of concern often have mutations to the spikes in particular.

Most attempts to make a universal vaccine involve trying to be a little less dependent on recognizing that single spike protein.

High-profile candidates include the American biomedical facility known as the Walter Reed Army Institute of Research, which, according to an interview in national security site Defense One, is attaching multiple spike proteins to each orb so that it can target different versions of the virus. While it remains in the very early stages of testing, early results have been promising.

Other researchers are hoping to get away from the spike protein altogether.

Among them is the McMaster team, whose inhalable virus is also designed to target parts of the virus other than the spike protein. Miller, who has previously worked on trying to make a universal flu vaccine, points to the way in which health authorities have to make an educated guess every year about which strains of flu to put in their annual flu shot.

“The issue with that approach is that you’re always, always, always going to be behind the virus, you’re always chasing it.”

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