What we know and do we need to do it?

The experiment was every parent’s worst nightmare – but it transformed medicine. In 1796, Edward Jenner, a country doctor in England, deliberately exposed an eight-year-old boy to one of the worst plagues of the era: smallpox. Jenner had observed that milkmaids suffering from its less dangerous cousin, cowpox, tended not to catch smallpox themselves. So he took pus from a cowpox lesion and scratched it into the arm of his gardener’s son. The boy felt a little sick but quickly recovered. Next, Jenner exposed him to the real thing: smallpox. And this time the boy didn’t get sick at all. Jenner had just invented what is considered the first vaccine. Two centuries later, smallpox became the first human disease driven into extinction thanks to mass vaccination.

Fortunately, safety standards and delivery methods have come a long way from cowpox pus but vaccines still work largely the same way. Instead of waiting for you to catch a pathogen to develop immunity, a vaccine trains your body to make the virus-fighting antibodies it needs by exposing you to a tiny (and, these days, harmless) part of the virus. While children have been the focus of most vaccination campaigns throughout history, in the case of the world’s latest plague, COVID-19, they are mostly last in line.

That’s because, unlike in many past epidemics, kids have a much lower chance of dying from this coronavirus than older age groups. And, unlike in 1796, vaccine trials on children are now generally conducted after those in adults, as dosages and other safety factors are considered with more caution. While millions of teenagers have already had their COVID shot around the world – from the mRNA vaccines by Pfizer and Moderna in the United States to a new needle-free DNA shot in India – trials for younger kids, from 12 years to six months, are still underway.

Many parents now hope the vaccines will help get their children back to school safely. So what does the science say so far? And when are COVID vaccines for kids likely to be on offer?

What do we know from trials so far?

Doctors aren’t quite sure why children seem to be mostly spared the worst of COVID-19 disease but the numbers tell the story all around the world. (Out of the more than 130,000 people who died of COVID in the UK during the first year of the pandemic, for example, just 25 of them were children.) That makes weighing up the risks against the benefits of a coronavirus vaccine in children especially delicate. For any shot to make it through approvals, the risk you may face from the unintended side effects must be a lot lower than the risk from the pathogen itself.

Australian kids already have very high vaccination coverage against disease, with about 95 per cent getting their recommended shots, such as for measles and polio. “We know it saves lives,” says paediatric immunologist Professor Peter Richmond. “We know it’s one of the best things you can do for your child and parents really value vaccination.”

Many past plagues, such as polio and the 2009 swine flu, have hit children hard. “So, for the last one, swine flu initial vaccine studies looked at children at the same time as adults,” Richmond says. “But with COVID, kids are not as big a concern [for severe disease] so we could wait till we had more data.” There was nothing sinister in the delay – “that’s standard” – says Richmond, who is head of the vaccine trials group at the Telethon Kids Institute and has been helping to analyse vaccine data from Western Australia.

So far, what data we do have looks good. Teenagers in wealthy nations such as the US and Canada have been widely vaccinated and received very high protection against COVID without raising any major safety concerns. In March, Pfizer claimed its vaccine was 100 per cent efficacious in those aged between 12 and 15, based on an unpublished clinical trial of 2260 adolescents. (No teen vaccinated in the trial got COVID).

In May, Moderna announced its shot, which uses the same mRNA technology, was 96 per cent effective at stopping COVID in those aged between 12 and 17 after just one dose and, as with Pfizer, did not have any serious safety concerns. Australia’s medical regulator the Therapeutic Goods Administration (TGA) has pored over the data for Pfizer and, in July, it followed the US, Canada and other countries in expanding its approved use to 12- to 15 year-olds as well as those 16 and over. Indigenous kids in that age group as well as those with underlying health conditions have already joined the roll-out and the remaining 12-15 year-olds are expected to be offered a shot by the end of the year. (Moderna, which was approved for adults only recently in Australia is likely to also be approved for 12- to 15-year-olds soon, as it is already in some other countries).

Children and teens generally respond very well to vaccines and the COVID shots don’t look to be an exception, Richmond says. “In trials, the 12-15s made even more antibodies [to kill the virus] than young adults. We saw that with the human papillomavirus (HPV) vaccine too.”

What do we know about vaccines in younger kids?

While 12- to 15-year-olds could receive the same dose of COVID vaccine as adults, researchers are now trialling the right amount for younger kids. With their smaller bodies, and immune systems that seem better prepared to fight off a case of COVID-19 than adults, experts think they should still get strong protection from a smaller dose, hopefully with fewer side effects. “We’re generally more cautious about checking how children tolerate vaccines,” Richmond says. “Sometimes we’ll start with a lower dose and slowly ramp it up to get the ideal protection.”

In the Pfizer and Moderna clinical trials, the first group of children vaccinated get the lowest dose, about a third the strength of the adult shot, and are monitored closely, before it is slowly increased in the next group.

In late July, America’s regulator the Food and Drug Administration (FDA) requested that trials of Pfizer and Moderna in younger children expand by thousands more participants, to better screen for rare complications too. Data from those trials are expected to land before the FDA in October or November, and America’s top infectious disease expert, Dr Tony Fauci, says there’s “a reasonable chance” that children under 12 there will be offered vaccines by Christmas, perhaps even sooner.

“Once it’s approved there, it could happen here and in Europe fairly quickly [once other regulators go through the data],” says Richmond. “I expect we’ll see Australian children vaccinated next year. It depends if they have to adjust the dose [in terms of] production and distribution.”

AstraZeneca’s own small trial in about 300 young kids aged between six and 17 was put on ice after the vaccine was linked to rare cases of a clotting condition called TTS in adults around the world, especially younger adults. That makes it an unlikely option for children, Richmond says. “If Astra was the only vaccine that we had, I’m sure we’d be running big trials in kids, but we’re being conservative. We know young people have a higher risk of that clotting.”

Meanwhile, China has already approved its own vaccines, Sinopharm and Sinovac, for children aged between three and 17 after early trials didn’t raise any safety concerns, and Russia has been trialling its Sputnik V vaccine, which uses the same viral vector vaccine technology as the AstraZeneca and Johnson & Johnson (J&J) shots, on young people.

J&J has flagged it wants to test its one-dose vaccine on younger children too. It has been linked to the same rare clotting disorder as AstraZeneca, at a much lower rate. Sputnik hasn’t, although some experts have questioned how well Russia is monitoring for those kinds of rare side effects.

Yes, what about these side effects?

Mild side effects are common for most vaccines and can affect both kids and adults. They are caused by your immune system responding to the shot. When your body spots an invading pathogen (or, in this case, a vaccine dressed up to look like one), its first generic line of defence – known as the innate immune system – launches into battle (your arm near the injection site might get sore and inflamed, for example). This first wave of attack takes care of most nasties and buys your body time to develop its second adaptive response – making antibodies designed to gum up and stop the specific virus in its tracks, as well as killer T-cells that will hunt infected cells.COVID vaccines introduce a tiny piece of the virus, the signature spike protein it uses to hack into our cells, to trip this immune response without infecting you. If the virus shows up for real, your body will already know how to eliminate it fast.

Many of the mild early symptoms of both viruses and vaccines (such as fever and aches and pains) are caused by that first innate response, explains ANU immunological researcher Professor David Tscharke. Everyone’s is a little different. While more than 90 per cent of adults in Pfizer and Moderna trials developed protective immunity against COVID, some people barely got a sore arm while others felt very sick. Our immune systems tend to peak in high school with puberty, Richmond says, so young people often have a stronger innate response compared to older age groups, and so are more likely to get mild side effects.

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If there’s a more serious side effect from a vaccine, it generally comes down to how our immune system has reacted too, and so it will show up early, within the first few months. “That’s why we don’t expect long-term side effects,” Richmond says.

The spike protein delivered by the vaccine is harmless, Tscharke adds, only one of 29 proteins that make up the real coronavirus. Some vaccines even need extra molecules added to them, known as adjuvants, so the immune system will recognise the piece of virus used as a threat at all. The mRNA vaccines Pfizer and Moderna, as with shots for measles and the flu, don’t need an adjuvant, Richmond says. Using technology that has been in development for many years, they insert one tiny segment of the virus’s genetic code (which is written in single-stranded RNA rather than our own double-stranded DNA) to wake up the body’s defences. That RNA is encased in a fatty nanoparticle that dissolves when it hits a cell. The cell then reads the RNA, instructing it to make the spike, which in turn, triggers the body to make the right antibodies to fight it.

All those spikes will leave the body fast too – themselves hunted down by the body’s killer T cells as immunity kicks in, Richmond says, “so it’s not going to lurk around”. And it can’t get entangled in our DNA either – that’s held in the nucleus of each cell, which the RNA does not reach.

As for rare complications, the scale and speed of the vaccine roll-out, the largest in history, means more adverse events are being picked up, even faster than normal. “These vaccines have been tested and monitored so intensely, the fact there’s been so few problems, including in adults and teens, is remarkable.”

While kids are unlikely to get the AstraZeneca shot linked to clotting syndrome TTS, the mRNA vaccines have been linked in very small numbers to inflammation around the heart, myocarditis or pericarditis. This has been reported in teenagers as well as adults, mostly in young men, “but still at a slightly lower rate in adolescents than the young adults”, Richmond says. The condition is generally mild; it’s more likely to do damage if you get it from COVID itself. “This inflammation sometimes happens in that young adult, teen, age group when they get a viral infection, so it might be a non-specific [immune] reaction to the vaccine,” Richmond says. “But that kind of viral inflammation doesn’t seem to happen in much younger children, so I don’t expect it to be as much of an issue in under 12s.”

For children, he says, there can be a concern the vaccine (or the virus itself) will trigger an “overreaction” of the immune system. In rare cases, fevers can get so hot, or change so rapidly, that it triggers convulsions in a small number of young children, generally those under five. The insulation around the nerve cells in their brain might not be developed enough, Richmond says, “and that electrical wiring can short-circuit” for a moment. This generally doesn’t cause lasting damage but will be watched for closely. In 2010, Australia’s seasonal flu shot had to be reformulated after it triggered a significant spike in these rare febrile convulsions among very young children, for example – more than 50 times the usual rate.

Both pregnant women and breastfeeding mothers, meanwhile, can be vaccinated without any harm to their babies (and the shots have no impact on fertility, although COVID itself might), Richmond says. For pregnant women, vaccination can almost become two-for-one protection, as virus-fighting antibodies will be carried through the placenta from mother to baby. “Breast milk may also pass some onto the child, but it won’t offer proper protection,” Richmond says.

But do we need to vaccinate kids?

Decisions to vaccinate come down to discussions between parents and doctors, but almost all experts agree kids should get the shot if trials give the all-clear. The question is when they will be able to. While other groups at higher risk from COVID remain unvaccinated due to limited supply around the world, Richmond says it’s right for kids to stay a lower priority.

Children are generally front of mind for public health responses, and parents are understandably concerned. “But [for COVID] the epidemiology has been that the younger you are, the less likely you are to end up with severe disease in hospital,” Richmond says. Of course, there will still be children who get sick from COVID. “And, if enough children get infected, some will end up in intensive care.”

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The Delta variant of the virus is at least twice as infectious as the original virus that first emerged in humans in late 2019, and that means everyone, including children, have a higher chance of catching it. With fewer young people vaccinated compared to older people, the age demographic is already shifting in some hospitals around the world. “It’s the situation they’re facing now in some southern states in the US where they’ve had very poor vaccine coverage in adults so there’s still an ongoing fourth wave of COVID despite the [faster vaccine roll-out],” Richmond says.

While kids are often protected if the adults around them are immunised, Richmond understands concerns that the virus may mutate to better infect children amid warnings that COVID is already becoming “a pandemic of the unvaccinated”. “It may become more of a disease of children. That’s why it’s important we do the studies now so that if it does shift and hit kids harder, we will be ready with data [to safely vaccinate them].”

National cabinet has agreed to start reopening Australia when 70 and 80 per cent of people aged 16 and over are fully vaccinated. At those levels, modelling by the Doherty Institute suggests public health measures apart from lockdowns, such as testing, tracing and quarantine, will be enough to contain outbreaks and bring down spread. But experts have been quick to point out that, with children left out, those targets represent just 56 per cent of the total population.

It is unclear how big a role children play in the spread of the virus. The Murdoch Children’s Research Institute has found that children aged over 10 transmit it at similar rates to adults (younger kids likely less); the Doherty modelling concluded vaccinating under 16s would have almost no effect on slowing down the virus in the broader community; and a review by Australian researchers in February said there wasn’t enough evidence to draw any conclusions yet either way.

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The science seems to suggest so far that outbreaks in schools are fuelled more by outbreaks in the community. Kids may even be more likely to pick up the virus at home than the classroom.

Vaccinating kids faster could speed up their return to school, after long, hard months of learning from home without seeing their peers or teachers. Still, many experts say the risks to children from COVID are too low to justify vaccinating young age groups while people at very high risk in the developing world still wait on vaccines. Rich nations hoarding early supplies mean it’s likely much of the developing world will remain unvaccinated for some time – leaving the virus another open window to evolve.