So we have vaccines. What happens now?

What might the next few years look like, as the population is gradually immunised but gaps in coverage remain?

“I’m one of those public health people who love silver bullets.”

As editor-in-chief of BMJ Global Health, and a health systems expert at the University of Sydney, Dr Seye Abimbola is well acquainted with the damage that SARS-CoV-2 has wrought around the world. So he’s understandably excited about the potential for vaccines to be the intervention that restores something approaching normality to the world.

Since their discovery, vaccines have been the closest thing to a silver bullet that modern medicine has come up with: a single injection – or maybe two – and an individual is protected for their lifetime against infectious pathogens that might cripple or kill. Even those not vaccinated can benefit from protection through herd immunity.

There was a gargantuian global sigh of relief as the first COVID-19 vaccines were shown to be effective, approved for use and finally deployed en masse. Leaving aside for a moment the sluggishness and supply problems besetting our own rollout, news and social media have been filled with images of politicians and celebrities getting vaccinated, and of joyful, mask-free reunions between immunised friends and family members. Vaccine clinics have been swamped. The overwhelming sentiment has been: “Great, now things can go back to normal.”

But neither the 1918 influenza pandemic, nor the first SARS-CoV epidemic, and not even the Ebola epidemics, have been brought to a satisfactory close with vaccines. The only disease to have been effectively wiped off the face of the earth with vaccines is smallpox.

The public health community has been a little more tempered in its jubilation. Even Dr Abimbola is realistic about what the COVID-19 vaccines will achieve. “I don’t think it’s going away, COVID-19,” he says. “But I think that the vaccines will put us in a place where we can live with very minimal casualties.”

The COVID-19 vaccines are no silver bullet.

“The vaccine, as we see it evolving in terms of effectiveness in the northern hemisphere, looks as though it will be a key weapon in our armamentarium,” says Professor Tania Sorrell, Director of the Marie Bashir Institute for Infectious Diseases and Biosecurity. “But it’s not the only one.”

One of the biggest questions about the impact of vaccines comes down to their effectiveness, not just at reducing severe disease, but also outright infection and, importantly for public health, transmission.

The Pfizer/BioNTech mRNA vaccine, which was the first to be approved in Australia, has shown nearly 95% efficacy at preventing symptomatic, confirmed COVID-19 seven days after the second dose was received.¹ The AstraZeneca vaccine has shown an overall efficacy of 66·7% in preventing symptomatic confirmed COVID-19, but this climbed to just over 81% when the two doses were given more than 12 weeks apart.² The Moderna mRNA vaccine, which has not yet been approved in Australia, shows 94% efficacy against symptomatic COVID-19 and 100% efficacy against severe COVID-19.³

These efficacy findings are on par with many existing vaccines for other diseases, but still don’t offer 100% protection against infection with SARS-CoV-2. Nor is there yet much evidence about whether these vaccines will reduce the risk of an infected vaccinated individual from transmitting the virus to another.

While vaccines might substantially – and perhaps completely – reduce the risk of severe disease, there’s still the risk of mild to moderate illness in a small number of those who are vaccinated. That also means there’s still the risk of long COVID: persistent, often crippling symptoms that last many months after infection.

The second issue with existing vaccines is SARS-CoV-2 variants. These are creating headaches for vaccine developers because the significant variants contain mutations in the virus’s spike proteins that it uses to gain access to human cells, and which are a key target for vaccines.

One study found the AstraZeneca/Oxford vaccine offered little protection against mild to moderate infection caused by the South African variant,⁴ and another found Novavax’s vaccine offered reduced protection against both the UK and South African variants.⁵

As long as the SARS-CoV-2 virus circulates in humans, mutations will occur: the greater the number of infections, the greater that likelihood is. “If they come up against a hurdle in the form of a vaccine, they mutate all the time,” Professor Sorrell says. This makes a strong argument for getting infection rates under control by any means necessary, because this will give vaccines their best chance at working.

The third issue is that not everyone is getting vaccinated at the same time. Most countries rolling out vaccines are doing so in a staged fashion, prioritising higher-risk populations such as the elderly and frontline healthcare workers.

While this is a practical response to the challenges of the biggest vaccination program ever undertaken in human history, it also leaves large sections of the population vulnerable to infection, and creates a reservoir of virus that can incubate further variants.

So far, no COVID-19 vaccines have been licensed for use in children younger than 16. Moderna has launched a trial of its vaccine in children,⁶ but the results of that are still some way off. While all the evidence suggests children have a lower risk of infection with SARS-CoV-2, a lower risk of serious and fatal COVID-19, and are less likely to transmit the disease, the persistence of the virus in this unvaccinated group could incubate further variants.

The rollout of vaccines globally has also been unequal. Vaccine nationalism reared its ugly head almost as soon the first vaccines began to show efficacy in clinical trials, with some countries – Australia included – pre-purchasing enough vaccine doses to immunise their entire populations and then some,⁷ while other countries were left begging. This means some countries will be left behind in the race towards global herd immunity.

For vaccines to truly get control of a global pandemic, there needs to be a global approach, says Professor Catherine Bennett, chair in epidemiology at Deakin University. “This combination of lockdown restrictions and vaccination rollout, we have to do it globally,” Professor Bennett says, “because if we end up with corners of the world that might have poor access to vaccine and quite uncontained epidemics, then you still got the risk of variants occurring”.

The COVAX initiative is an attempt to avoid this. This joint initiative of the WHO, GAVI – the global vaccine alliance – UNICEF and the Coalition for Epidemic Preparedness Innovations, strives for “fair and equitable access for every country in the world” by supporting procurement and delivery of COVID-19 vaccines to low and middle-income countries. To do this, COVAX is aiming to raise around US$2 billion from sovereign donors. So far, it has raised around US$700 million.⁸

Dr Abimbola says the global nature of a pandemic poses a moral challenge for the leaders of wealthier nations, but the response so far suggests things have come a long way since the start of the HIV/AIDS crisis.

“We seem to see one another in the world more clearly than we used to and take casualty and lives much more seriously,” he says.

But it can still be a tough sell to politicians who have their own electorates to answer to about vaccine availability. “There is, I think, a certain political lack of understanding of what it means politically to be to be generous and to do the right thing,” Dr Abimbola says. Prime Minister Scott Morrison has arranged for 8000 doses of the AstraZeneca COVID-19 vaccine to be sent to Papua New Guinea, which is experiencing a severe resurgence in infections, and has flagged sending one million more.

He believes there is a political argument to be made that wealthy countries have an interest in ensuring that low- to middle-income nations have equitable access to vaccines, if they ever hope to be able to open borders for international trade and travel. “We are going to get into the business of helping them vaccinate themselves,” he says.

However, as a third wave of the pandemic hits Europe, and hospitals reach capacity in Brazil, that time may not yet have come. “I feel politically that we need to get out of a gloomy place first.”

Given all these caveats, what might the next few years look like, as an increasing proportion of the population – nationally and internationally – is vaccinated but gaps in vaccine coverage remain?

A recent report from the Australian Academy of Health and Medical Sciences on Australia’s path through the COVID-19 pandemic argued that even as vaccines are rolled out, the nation will still need to maintain public health measures including high levels of testing, contact tracing, isolation, quarantine, face-mask use and physical distancing.

“This is going to be our new learning journey: how we transition to thinking of COVID as another endemic, probably seasonal infectious disease that is going to be here but we’re going to have vaccines to prevent that burden of suffering and death,” says Professor Jodie McVernon, director of Doherty Epidemiology at the Doherty Institute.

“It will be a careful unpeeling of the fingers here, because we’re starting from this incredibly privileged position of no community transmission, but a fully vulnerable population.”

Professor McVernon argues that the Australian population can’t let down its guard yet: we still need to be engaged with and accepting of public health and social measures to reduce transmission. “We need the Australian population to keep thinking collectively and cohesively as they have, because that’s why we’re where we are,” she says.

Professor Bennett says that good vaccine coverage across the nation will mean that if the virus does get out, it won’t go far. But that control will rely on the same measures that have been used so far to eliminate outbreaks, and those measures become even more important if – or when – a new variant arrives in Australia that is not covered by the vaccine.

“We might still need some relatively proximal precautions, like your mask and hygiene and distancing, and we might step those up a bit if we know the virus is out there, but we won’t need to go to the much more stringent lockdowns to contain it,” she says.

The importance of testing and contact tracing will remain, particularly with the threat of new, more infectious variants, Professor Bennett says. She gives the example of two separate seeding events in two quarantine hotels Victoria during the second wave, one of which was later discovered to be caused by a variant with similar mutations to the more transmissible UK variant. However that particular seeding event only resulted in 37 cases, while the other original variant ran rampant.

The different behaviour of variants might also require contact tracing and quarantine systems to be adaptable, particularly if the variants have different incubation periods.

“What is being questioned is whether once you’re infected, you might stay infected for longer, because it’s just harder to defeat this virus as quickly,” Professor Bennett says. There have been recent cases of travellers released from their quarantine period after testing negative, only to test positive a day or two later.⁹

“if they’re infectious for longer – particularly if they haven’t been identified, tested, captured by the system and isolate – if they’re out there, and now they’re not infectious for five to seven days, but they might be infectious for 10 days: all those things just change the picture.”

Australia’s international border controls have been some of the strictest in the world, restricting entry by international travellers, cruise vessels and restricting outbound international travel by Australians. The federal government recently extended the human biosecurity emergency period by a further three months, to 17 June, recognising that “the COVID-19 situation overseas continues to pose an unacceptable public health risk to Australia, including the emergence of more highly transmissible variants”.¹⁰

But those borders can’t stay closed forever, and there is increasing pressure to reopen to international students and for international sporting events. How might that be managed in a COVID-endemic world?

One solution being examined is the notion of vaccine or immunity passports: individuals who have antibodies to SARS-CoV-2 – whether gained through infection or vaccination – are given greater freedom of movement because of their presumed lower risk of infection and transmission to others.

But this isn’t a straightforward as it appears, says Proferssor Sorrell. “We can’t strictly say, ‘because you’ve been immunised, there is zero chance of you getting another infection’,” she says.

Immunity passports could be used simply to indicate that an individual has received the vaccine – which is relatively limited information given the range of immune responses to immunisation – or a passport could contain more detailed information about the nature of their antibody response, such as the presence or levels of neutralising antibodies. Qantas has already flagged that it will require proof of vaccination for passengers once international air travel resumes.¹¹

Dr Abimbola acknowledges that, for all the potential flaws and uncertainties around vaccine passports, they probably will emerge as borders reopen. However he also sees the possibility of testing and vaccination points in airports, such as already exist for yellow fever in parts of Africa. Many countries, including Australia, New Zealand and the United States, already require pre-departure testing within 72 hours of flight departure, and proof of negative RT-PCR result at the time of check-in.¹²

Another area that many argue needs continued focus even after the rollout of vaccines is treatments for COVID-19. The Australian Academy of Health and Medical Sciences report noted that there is a relatively limited number of effective treatments for COVID-19, including respiratory support, corticosteroids and – with some caveats about the certainty of evidence – remdesivir.

“Further research is vital if we are to increase existing treatment options, further reduce COVID-19 associated morbidity and mortality, and find treatments that work in milder cases, early disease or even prophylactically,” the report’s authors wrote.

Despite all the uncertainty, the simple fact that effective, safe SARS-CoV-2 vaccines were being rolled out less than a year after the first emergence of the virus is astounding.

Professor McVernon says that at the start of the pandemic, “I hoped with optimism that vaccines might appear, but the fact that we have them, and they’re being rolled out in the numbers they are right now, to me that’s just extraordinary.”

But she also warns against being complacent. “This is not done and dusted yet,” she says.

“2020 was a year of learning and learning and learning again, and being adaptive and bringing in new evidence and using that to shape more effective responses. And we’re going to be doing all of that again in 2021.”

So we have vaccines. What happens now?

References:

Opioid trial in Lancet wins ANZMUSC gong

‘Breakthrough’ mAb in moderate to severe bullous pemphigoid

New option for psoriatic arthritis and axial spondyloarthritis

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