n June 2021, Israel’s early lead in the world vaccination race seemed to be crumbling. Months earlier it had been the real-world laboratory that showed the effectiveness of vaccines in crushing COVID-19 outbreaks. But now a surge of the faster-moving Delta variant was taking hold, including among the double-jabbed. Data indicated that people vaccinated back in January were more likely to catch COVID than those vaccinated later. Protection from the vaccines seemed to wane after six months.

By September, with new cases topping 10,000 a day, Israel had started rolling out booster shots. At the time, scientists were split over whether a third dose was needed – and the World Health Organisation warned against using up vaccine on boosters while so much of the developing world was still without a single dose.

But, for Israel’s caseload at least, it paid off. The numbers fell again, and studies have since shown that a booster of mRNA sharply lowers the likelihood of COVID infection. With another variant, Omicron, on the loose, the UK, the US, Europe, and now Australia are also turning to boosters, generally six months on from a second dose.

So what does the science say about boosters, why are we mixing and matching vaccine brands and how many more are we likely to need?

Why do we need boosters?

Vaccines teach your body to make special immune cells that can defeat the virus fast if it gets into your system (those are proteins known as antibodies to gum up the virus and killer T-cells to hunt down infected cells). “However healthy your immune system, your body still takes a while to recognise and fight a new threat like [COVID],” says Professor Seshadri Vasan who has spent the pandemic trialling vaccines and tracking coronavirus mutations at the CSIRO’s dangerous-pathogens lab.

Two doses of vaccine give you a big surge in these antibodies as well as longer-lasting memory B and T cells to patrol your body for future infections. A fortnight after full vaccination, the two mRNA vaccines Pfizer and Moderna are about 90 per cent effective at stopping symptomatic COVID cases, and AstraZeneca about 70 per cent, even against Delta. But the real strength of all the approved vaccines is in stopping severe disease from the virus – on that measure, they are close to 100 per cent effective. A US study found that an unvaccinated person was 29 times more likely to end up in hospital from COVID than someone who was vaccinated, while almost all the COVID patients in intensive care during Australia’s delta surge haven’t been vaccinated.

Still, this immune memory does fade over time, particularly in older people. Respiratory viruses such as COVID are notoriously difficult to immunise against to begin with, says infectious disease physician Associate Professor Paul Griffin. “We don’t tend to get lifelong protection, even after we catch the common, milder coronaviruses that give us colds. So we always thought we’d need boosters to top up our immunity. What we didn’t know was when.”

The good news is that while people have a higher chance of being infected with COVID six months or more after their second dose, protection against developing a severe case does not decline nearly as fast. To gauge the effectiveness of a vaccine, scientists usually measure antibody levels in someone’s blood. But Griffin says this doesn’t give the complete picture. Antibodies naturally wane over time. “It doesn’t mean the capacity to produce them has gone,” he says. And, while falls in antibody levels may make it easier for a virus to gain a foothold in the body, there will likely still be T cells on the prowl – which are harder to measure but particularly important at stopping severe disease.

In May, Australian researchers calculated that when a vaccinated person’s antibody levels fell to about 20 per cent of their previous level, protection against getting COVID dropped to 50 per cent. But protection against a severe case didn’t fall to 50 per cent until those antibody levels had plunged to just 3 per cent of what they had been.

“The case for boosters is not a failure of the vaccines,” says Griffin. Many existing vaccines need boosters – they both build up antibody levels again and improve the body’s longer-lasting immune defences. COVID boosters can get immunity levels up even higher than where they were two weeks after the second dose.

“The scientific community is actually now debating whether three doses [instead of two] should have been the primary dose schedule all along,” adds Vasan.

With the pandemic still raging, Griffin says,“we’re mostly boosting to stop the spread” of the virus right now. “We are fortunate to be in a position in the West where we can use boosters to optimise people’s immunity when there’s lots of transmission happening or a new variant we’re worried about.”

When should you have a booster?

Based on both trials and real-world data overseas, Griffin says six months after a second dose has emerged as the standard time to get a booster in Western countries with good access to vaccines such as Australia and the US. (The WHO has yet to recommend widespread boosters.)

As with the original vaccine roll-out, vulnerable groups are at the front of the booster queue. Many Australians with compromised immune systems have had third doses already (at a minimum of two months after their second), and older people and frontline workers who were vaccinated more than six months ago have been getting them too. In November, Australia followed Israel in opening up boosters to every adult six months after their second dose, no matter what vaccine they had already had. As of December 7, 678,154 people were already eligible for an mRNA booster, and, of those, 559,046 had received a third dose of vaccine so far. By the end of the year, 1.75 million people will be eligible and that number will grow to 4.1 million by the end of January, 7.5 million by the end of February before ballooning to 17.8 million by the end of May.

Meanwhile, in places such as the UK, the entire boosters program has been brought forward from six months after your second dose to three as concerns grow that the highly mutated Omicron variant may be better able to evade vaccines. Australia’s expert vaccine advisory group ATAGI considered shortening the interval here too but decided there wasn’t enough evidence that an earlier booster would improve protection against Omicron. The group did advise that the interval could be shortened to five months for logistical reasons, such as for “patients with a greater risk of severe COVID-19 in outbreak settings” but noted this: “There are very limited data on benefit for boosters given prior to 20 weeks after completion of the primary course, and the duration of protection following boosters is not yet known.”

For Australia, where much of the population is still freshly vaccinated, Griffin says waiting the six months will mean many people will be vaccinated around Easter next year right ahead of winter (when the virus may flare up again in the cooler weather). “So I think that’s the right time.”

Boosters are not mandatory in Australia but they are strongly recommended after six months (even if you’ve already recovered from a case of COVID, a federal department of health spokeswoman confirmed). While in countries such as Israel the definition of “fully vaccinated” has now shifted from the original two doses to three, the Australian government says two doses is still enough to access vaccinated-only spaces in the reopening such as bars and restaurants. Reminders for people to book in their third dose six months after their second will be sent to millions of Australians via the MyGov government portal, and the government says its modelling shows that there will not be supply shortfalls again.

Are the boosters updated to cover new variants?

Not so far. Vaccine makers have been preparing how best to tweak vaccines for new variants for many months now. But when many existing formulas were found to still work well against the now dominant Delta strain (which emerged in late 2020), regulators approved them as third dose boosters. Some experts have since wondered if that was a missed opportunity but Dr Peter Marks at the Food and Drug Administration (FDA) in the US, where both Pfizer and Moderna are made, has said that changing formulas only when it is really necessary means less “churn and burn” on manufacturing, and so fewer delays in getting boosters out.

Now, scientists around the world, including Vasan at the CSIRO, are poring over samples of the new variant Omicron to see if a tweak is needed this time. Omicron has about twice as many mutations as the highly infectious Delta, including 34 in the crucial spike protein that the virus uses to hack into our cells. But it is still unclear how that will change its behaviour in patients. Vasan describes it this way: “Just because you might understand individual personality traits, doesn’t mean you can predict exactly how someone will behave. We understand a lot about some of these mutations because we’ve encountered them before in other variants, but Omicron has new ones too, and how they all work together could be different.”

So far, South African doctors report many of the new Omicron cases are mild but the speed at which the new strain has exploded across the continent suggests it is highly infectious. Scientists are particularly concerned the new variant’s spike might have changed shape so much that antibodies can no longer stop it in its tracks (and the WHO has said that reinfection appears more likely with Omicron than Delta). But Vasan adds, “There’s not a one-to-one correlation between the number of mutations and resistance to vaccines.”

There’s also no set threshold of protection against a variant below which vaccines are said to need updating. This is evolving itself, Griffin says. “Most of us are expecting at some point we’ll have to tweak. And whether Omicron is the time or not, people will be surprised how fast it can happen.”

The mRNA vaccines are the easiest to adapt, he says. They show our body a tiny segment of the virus’s genetic code (known as RNA) – in this case, the spike protein – to train our immune system to make the right antibodies to fight it if it ever shows up for real.

To tweak the vaccine, scientists just need to swap out the original spike RNA for a mutated Omicron version in its nanoparticle casing. BioNTech, which makes Pfizer, says it can produce and ship an updated version of its vaccine within 100 days if Omicron requires it. But its CEO, Ugur Sahin, has so far been more optimistic about existing vaccines holding up to the variant than the head of Moderna, Stéphane Bancel, who told the Financial Times that he expects to see a “material drop” in vaccine effectiveness against Omicron.

In Australia, tens of millions of the booster doses on order are not expected to arrive until next year, and those may be tweaked if companies such as Pfizer decide that an update against variants is needed. Department of Health secretary Professor Brendan Murphy told a senate committee on December 7 that the country’s contracts already “envisage that if a very different vaccine is required those advance purchase agreements cover that”.

Read the Article

News

Stem Cell Membrane-Coated Nanoparticles in Tumor Therapy

Cell membrane-coated nanoparticles, applied in targeted drug delivery strategies, combine the intrinsic advantages of synthetic nanoparticles and cell membranes. Although stem cell-based delivery systems were highlighted for their targeting capability in tumor therapy, inappropriate [...]

Self-Healable, Human-Like Artificial Skin

Self-healable ionic sensing materials with fatigue resistance are imperative in robotics and soft electronics for extended service life. The existing artificial ionic skins with self-healing capacity were prepared by network reconfiguration, constituting low-energy amorphous [...]