Secret killer hiding in the flu virus

Millions of people who die with the flu aren’t killed by the virus. Instead it’s a ‘Jekyll and Hyde’ bacteria. But in a revolutionary breakthrough, SA scientists are about to begin human trials on a vaccine that will wipe out this secret killer forever.

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Jacinta Foulds was a 35-year-old mother of three who didn’t think the flu vaccine was necessary for healthy people like her.

Yet, two weeks after falling ill with the virus, she was dead.

Within 24 hours of being taken to the hospital in Toowoomba, on Queensland’s Darling Downs, her body succumbed. Her final words to her husband, Dan, was an apology for the fuss and “I love you”.

Jacinta Foulds.

“We thought it would pass and she just needed to look after herself, but it didn’t pass,” a distraught Dan Foulds told The Courier-Mail newspaper after his wife’s death.

“On Tuesday she called me at work saying she definitely was not OK and I raced home right away. I took one look at her and rang the ambulance. The journey to the hospital was a Code One — critical with lights and sirens. Her heart crashed and I was told she could die. Seriously, how could a 35-year-old fit woman die from the flu?”

But Foulds, strictly speaking, didn’t die from the flu.

She died from a secondary infection that led to pneumonia. So far this year more than 662 people nationally have died from flu-related illness — including 103 in SA — and, if history is a guide, perhaps half the deaths would have been caused by those secondary infections.

This story is about the little known killer that causes most of them.

Its name is Streptococcus pneumoniae, or pneumococcus, and it’s one of the biggest bacterial killers on the planet. Now, in one determined Adelaide scientist, it may have met its match.

James Paton, one of Australia’s leading bacteriologists, has been tracking pneumococcus for 40 years and he believes he and his team have finally worked out how to exploit its weaknesses. If they are right, they are on the cusp of creating a revolutionary new vaccine that would potentially save millions of lives around the world — and make billions of dollars.

Pneumococci live in the nasal passages of up to 90 per cent of us, and usually cause little more than the odd sniffle.

But, a bit like Dr Jekyll and Mr Hyde, it can switch quickly into something potentially lethal — in this case when the body’s immune systems are compromised by flu, when pneumococci take the chance to invade.

The great Spanish flu pandemic of 1918-20, originally thought to have killed 40 million people, is now estimated to have killed closer to 100 million — many more than died in World War I. “And probably half of those deaths were caused by secondary bacterial infections,” says Paton.

Most of them, he adds, fell to pneumococcus.

“It’s a partner in crime with the flu virus,” Paton says of his nemesis. “It’s usually benign, but once the flu makes you sick, it takes the opportunity to attack.”

It lives in our nasal passages. “It wants to hang out in there and then if it causes a bit of irritation and inflammation, so you are getting a few more nasal secretions, that means it gets shed,” Paton explains.

“So if you sneeze it can be transmitted from person to person. There are billions of people who carry pneumococci in their nasopharynx at any one time.”

He says it doesn’t mean to kill us because “dead people don’t sneeze”, but some of us will naturally be more vulnerable. Yet even if it kills a few million people a year, that’s only one person in 1000. The bacteria can, literally, live with that.

Paton, from the University of Adelaide’s Department of Molecular and Biomedical Science was the 2017 SA Scientist of the Year, and heads the University’s Research Centre for Infectious Diseases. He has been tracking pneumococcus for four decades.

When he started as a young bacteriologist at the Adelaide Children’s Hospital in 1980, little was known about the bug. It killed a lot of people, but nobody really knew how.

Paton has made it his life’s work to find out.

Now he may be on the cusp of disarming it completely with a radical new vaccine, called Gamma-PN, that would potentially neutralise the deadly bug.

Of the 2-3 million people a year who die from the bacterium — mainly from pneumonia — most are over 65s or children, especially in third world countries.

But many millions more suffer other illnesses.

It also causes middle ear infections, particularly devastating in Aboriginal communities in Australia, and which can contribute to deafness; and it can also strike the brain, causing potentially fatal meningitis.

Professor James Paton has developed a vaccine that would protect against infection from all pneumococcus. Picture Matt Turner

Vaccines work by exposing our immune systems to a benign version of a bug that might infect us. British doctor Edward Jenner worked this out in the late 1700s.

He knew milkmaids rarely got smallpox, a disease that at times killed 20 per cent of the population.

But they did get cowpox, which he suspected was a milder version of smallpox. Jenner took pus from cowpox blisters and used it to inoculate a young boy — priming his immune system. When exposed to smallpox the child never fell ill. The word vaccination comes from the Latin vacca for cow.

When our body is hit with the flu, if we’re vaccinated, our defences already know what the invader looks like and so can speedily attach themselves to it.

Without a vaccination, the body isn’t clear what it’s defending against, so its first response is to launch a general, widespread counter-assault. Meanwhile, the virus may infect our throats, respiratory tract, even the lungs. At this stage, we’re feeling unwell not just from the virus, but our immune system.

The flu virus is tiny, and cannot survive by itself; instead, like the creature in the Alien movie, it grows inside our cells like a parasite, bursting out to spread itself.

In response, the body targets its own cells to kill the virus, and that alone can make you ill. We get headaches, inflammation, fatigue. In some people, the immune system overreacts to the viral threat and unleashes an early storm of attack so intense it kills them.

Inflammation and direct damage to the respiratory tract also enables those sleeper cells of pneumococcus bacteria to spread from the nasal area into deeper tissues, potentially causing pneumonia in the infected lungs, and can then spread to the blood.

“Those who die quickly generally die of the [flu] virus,” Paton says of flu-related deaths. “But after four or five days it’s the bacteria that kills them.”

Currently, both our flu and pneumococcus vaccines are far from perfect.

The flu vaccine needs annual updating, to try to match the various strains of the virus known to be circulating in the population (and would be useless against a completely new strain).

The pneumococcal vaccine, which is relatively new and given to children, only covers 13 of 98 known strains.

But Paton’s vaccine aims to give our immune system’s defenders a very clear picture of all 98 strains of pneumococcus in advance. It was developed from work by Paton’s colleague Dr Mohammed Alsharifi, an expert in viruses, who has simultaneously been working at the university on a super vaccine for influenza.

Most vaccines use chemicals to kill the live bacteria or virus, creating extensive collateral damage to the surface structures on the bug. That gives our immune system only a blurry image of what it must find. The new vaccine provides a kind of high definition facial recognition technology.

Alsharifi’s method does this by using gamma radiation to destroy the genetic material of the bug, thereby killing it, but keeping the bacteria or virus intact with undamaged proteins on their surface.

Until now, what has made pneumococcus so difficult to counter is that it is a master of disguise, hidden under a capsule. But when it latches on to our cells to start invading, it has to lower that capsule and expose itself. That’s when defenders can strike — if they know what to look for.

With the vaccine, says Paton, “we’re giving the immune system a damn good look at them rather than just a fleeting glimpse”.

Pneumococcus or Streptococcus Pneumoniae is a common host found in the mucosa of the mouth and pharynx.

While this would be an extraordinarily important global health development, it’s only half the story. Paton and Alsharifi hope to one day put the two vaccines together.

“We see the potential to deal with the world’s worst respiratory virus and the world’s worst respiratory bacteria at the same time,” Paton says.

It would, he says, be the best protection possible against a repeat of the Spanish flu pandemic that killed up to 5 per cent of the global population a century ago.

“I think you’d be in a very good position to prevent the sort of mayhem that could happen in the context of a global flu pandemic,” Paton says.

“Every few decades you have a re-assortment of the flu virus.”

While pneumococcus only lives in people, the flu virus also lives in pigs and birds. Paton explains that the influenza genetic material comprises seven fragments, and that if two different types of the flu virus infect the same cell (perhaps a human and pig version in a farm worker) then a new virus may result with six bits of one strain and one from the other. Thus, a pig-derived flu strain that human immune systems have never seen before may acquire genes enabling it to flourish in us.

“And that’s what happened during the great pandemic we presume, and the Hong Kong flu in the 1960s,” he says.

“So we’ve got no learned response to it. It’s not part of existing vaccines.

“Our vaccination strategy would be better able to cope with this scenario than any other. But if you’re going to get effective protection against mortality on the scale of the 1918 pandemic, then you are going to need to protect against both virus and bacterium.”

At this stage, Paton’s vaccine is more advanced in development, and is now approaching human trials.

Two years ago, their commercial partners formed a new biotech company, Adelaide-based GPN Vaccines Proprietary Limited, to translate the vaccine research into reality.

After testing on animals the vaccine is now being produced in bigger quantities.

“The next runs will be full production size, up to 300 litres, which would give you tens of thousands of doses,” Paton says.

Professor James Paton, the Director of the University of Adelaide’s Research Centre for Infectious Diseases. Picture: Supplied

The company now needs to raise $5 million to fund a human trial mid-next year: it plans to recruit 100 volunteers to test for safety and dosage, to ensure no ill-effects and to work out how much of the vaccine is needed to provide immunity in humans.

If all goes well in the first trial phases, a full blown efficacy trial would be needed. That could be as soon as in three years. But, for that, involvement of a major pharmaceutical company would be needed.

“We have to de-risk the project before we can attract a big pharma company — it could cost hundreds of millions of dollars to do a phase three trial,” he says. “Once you’re beyond Phase 1, that’s when you can have meaningful discussions with a manufacturer. You’ve shown it’s safe, you’ve shown it elicits an immune response.”

Such trials are huge. “You’re vaccinating up to 10,000 people to see what happens in natural acquisition of disease relative to a suitable control group, such as one of the currently licensed pneumococcal vaccines, which, unlike ours, cover only a limited number of the 98 known strains of pneumococcus,” he says.

“Given that the strains covered by the current vaccine are becoming less common, it would be feasible to compare our vaccine combined with the existing vaccine versus the existing vaccine on its own.”

Of course, after battling this bug for 40 years, Paton isn’t claiming victory yet. He says he knows the vaccine works in the laboratory, but he also knows many trials on mice or other laboratory animals fail when it comes to humans. Still, he’s more than hopeful of success: it could be three years but hopefully less than five.

And after spending a career tracking this bug, he feels very close to potentially putting it out of business — or, at the very least, seriously degrading its lethality. It’s exciting, he says.

“You are actually seeing the light at the end of the tunnel — and you know enough about it to know that it’s not the headlamp of an oncoming train.”

Originally published as Secret killer hiding in the flu virus