COVID vaccines: where the bloody hell are we?

Australia’s vaccine rollout program is now being overhauled due to new recommendations regarding the AstraZeneca vaccine.

Based on the advice of the Australian Technical Advisory Group on Immunisation (ATAGI), the Federal Government has recommended that people under 50 preferentially receive the Pfizer vaccine over AstraZeneca. This follows similar decisions made by regulators in Germany, Norway, Canada, the UK and other countries where the vaccine is being administered.

The recommendation comes after reports of serious side effects of blood clotting disorders, mostly associated with younger people.

According to Australia’s Chief Medical Officer Paul Kelly, the effects are very rare.

“It seems to be around four to six per million doses of vaccine,” he said at a press conference on 8 April. 

“It’s only been found in the first dose of the AstraZeneca vaccine, usually within four to 10 days after that vaccine. But it is serious and it can cause up to 25 per cent death rate when it occurs.”

It’s important to note that all vaccines and medications have adverse effects – even the flu vaccine – and the risk of developing these particular side effects is very low.

“For context, the risk of dying from a motor vehicle accident in Australia in 2018 was five in 100,000,” explains Rob Grenfell, CSIRO’s Health and Biosecurity Director. “The risk of death from COVID in people over 30 years old is one in 900, and for those over 50 it’s one in 90. And ‘long COVID’, where debilitating symptoms last for months after initial infection, is a real concern.”

However, Grenfell notes that since Australia is currently in a fortunate position regarding COVID outbreaks, we are able to exercise an abundance of caution. “The principal reason is that the risk-benefit ratio switches as you get younger, especially when there is a very limited risk of contracting the virus at this stage in Australia,” he explains.

In countries such as the UK, which has recommended against the AstraZeneca jab for people under 30, a more urgent situation requires a very different balancing of adverse effects versus the benefit of vaccination.

But what does this decision mean for Australia’s vaccination rollout plan? It’s already in disarray, with numbers lagging behind what was promised; we fell 3.4 million inoculations short of the end-of-March target. An analysis by the Guardian has estimatedthat completing the rollout at the current rate would take years. So will limiting who receives the AstraZeneca vaccine further delay the timeline?

Brendan Murphy, Secretary of the Department of Health, has said that the rollout will not be greatly affected in the next few months: the elderly will continue to receive the AstraZeneca vaccine, and while there may be delays in administering the Pfizer vaccine to health care workers under 50, he still promises that all of those “vulnerable to severe COVID will be covered as we planned by the middle of the year”.

But what will happen as we look to vaccinate younger people? Will we need to diversify the vaccines we administer? What do we currently know about which vaccines we’re using, and which alternatives we could soon have access to? Let’s break it down.

AstraZeneca

The Oxford-AstraZeneca vaccine is one of the two vaccines currently approved and being rolled out in Australia. It’s also the only one being manufactured here in the country, with the CSL Broadmeadows plant in Melbourne on track to soon produce 1m doses per week, and 50m in total across the year. 

But the reports of the rare side effects from the AstraZeneca vaccine – and the decision to recommend against it for those aged under 50 – may influence whether or not we continue to rely on it to reach our vaccine rollout targets. More than 11 million Australians are aged between 18 and 50 in Australia, and so following government advice we would need at least 22 million doses of an alternative vaccine to fully cover this section of the population.

Currently, CSL seems to be continuing to meet its targets and fulfil its contract of producing 50m doses by the end of the year. But will all of these doses be used if a large segment of the population seeks an alternate vaccine? If not, what will we do with them?

Pfizer

The Pfizer vaccine is also approved and being administered as part of Australia’s vaccine rollout. As of 8 April, Australia had purchased 20 million doses and received nearly 900,000 of them, but the federal government has just announced that they have secured a further 20 million doses.

“It is anticipated that these additional 20 million doses will be available in quarter four of this year, that’s our current instruction,” said Prime Minister Scott Morrison in a press conference on 9 April.

This will come at an extra cost, as the Pfizer price tag is higher – their price per dose is not capped like AstraZeneca.

Additionally, unlike AstraZeneca, we must import Pfizer. It’s an mRNA-based vaccine, which means it requires a different technology to manufacture – technology that Australia is not currently equipped with. While Pfizer has factories in the US, the Australian supply would likely come from Belgium and Germany.

This raises the question of export issues. Tough export controls introduced by the EU have so far prevented Australia from importing 3.1 million doses of AstraZeneca due to conflicts with meeting supply demands in Europe, though it remains to be seen if Pfizer doses will face the same issue.

Relying on imports may also pose an issue when considering how the logistics of Australia’s vaccination program might change if we come to rely on Pfizer. Like AstraZeneca, the Pfizer vaccine requires two doses – but while AstraZeneca requires the doses be administered up to 12 weeks apart, the window between Pfizer doses is much smaller: just three weeks.

In addition, as several experts have pointed out, the Pfizer vaccine also has side effects, including a small risk of anaphylaxis.

“Switching individuals from the AstraZeneca vaccine to the more costly Pfizer COVID-19 vaccine may also prove problematic with five cases of severe allergic reaction per one million doses being reported,” notes Roger Lord, from the Australian Catholic University and the Prince Charles Hospital in Brisbane. “These allergic reactions, like the unusual blood clots, are extremely rare and specific risk factors with use unknown.”

Novavax

The third pillar in Australia’s vaccination strategy is the Novavax vaccine. Australia has ordered 51m doses, but a timeline wasn’t inked into the contract, so when we might see these doses is unclear.

Although it has been granted provisional determination by the Therapeutic Goods Administration (TGA), Novavax is now seeking provisional approval, which is required before any doses can be administered. Phase 3 trials are still ongoing in North America and it’s estimated that approvals may not be obtained until the end of the year – or the third quarter of the year (July–September) at the very earliest.

The doses would be manufactured in the US or Europe and imported. But in theory, it could be manufactured in Australia. It’s a protein-based vaccine, and CSL has said they could feasibly produce doses – but only after its AstraZeneca program is complete, as producing the two side-by-side would be challenging in terms of logistics and safety. But with the government’s new recommendations about alternate vaccines for those under 50, could this change?

Other vaccines

Australia may now look to diversity its vaccine portfolio – which is long overdue, according to Nikolai Petrovsky from the College of Medicine and Public Health at Flinders University.

“Independent vaccine experts including myself have repeatedly told the government that it was extremely risky to put all their eggs in the one basket in backing just a few select vaccines associated with CSL,” Petrovsky says. “This was particularly high risk given the selected vaccines were based on completely novel technologies never before tested in humans. This advice was unfortunately ignored.”

Other contenders to consider include Moderna (an mRNA-based vaccine) and Johnson & Johnson (a one-shot vaccine), but Australia has not signed contracts with either of these companies yet. The government says they have been in discussions with Johnson & Johnson, which has also begun an approval process with the TGA and is at the same stage as Novavax. Both Moderna and Johnson & Johnson would need to be imported. 

It may also be time we looked at re-engineering the molecular clamp vaccine technology that was developed in Queensland last year – as well as to develop the capacity to manufacture other types of vaccines onshore.

Petrovsky says that the absence of a successful and diversified vaccine industry in Australia is a real problem.

He notes: “It is only by Australia developing such a diversified local vaccine development and manufacturing capacity that we can stop our dependence on the uncertain supply of overseas produced pandemic vaccines, thereby ensuring Australians are at the front rather than the back of the line when it comes to access to the very best vaccines.”

So what now?

There are many unanswered questions, even with Australia securing 20 million more Pfizer doses. 

Is the best course of action for CSL to continue producing AstraZeneca doses? Will it be necessary for them to pivot to Novavax, and how quickly could they do so? Will we see any export issues with the Pfizer doses?

Plus, there is the question of whether this will impact public confidence in vaccines.

“The fluid changes to recommendations are a serious challenge to the general public’s acceptance of immunisation, and will require a concerted effort to maintain it,” says Grenfell. “In Australia we have not experienced the full destructive force of the virus, so it is hard for the general public to comprehend the urgency for immunisation.”

Ross Gordon, from the Queensland University of Technology, adds: “People appreciate timely, clear, transparent, easily understood and honest information on which to base their health decisions. Unfortunately, this has been lacking so far in the Australian vaccination strategy.”

Looking long-term, experts are also warning that new or updated vaccines may be needed within a year as more mutations crop up – especially in developing countries where lack of vaccination will allow COVID to continue to spread and produce variants. It is unclear if this will be factored into Australia vaccination plans, particularly as the rollout may stretch past the end of 2021.

Initially, the plan was to fully vaccinate all Australians by October 2021, though plans were revised to administering at least one dose per person by October. Now, the timeline is even murkier – though the addition of 20 million more Pfizer vaccines means that the country will now, eventually, have access to 170 million doses.