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Vaccines

Australia needs herd immunity

The Oxford/AstraZeneca vaccine won’t deliver it

A long time ago, I used to drive a Holden Camira. It wasn’t the best of cars, but it got me where I needed to go. Until one day it didn’t. As I stood by the side of the road, watching oil bubble through the blown head gasket, a carload of yobs drove past. As they did so, they cheerfully offered some unsolicited commentary on how the Camira was not known for reliability. These days, I drive a Toyota.

What does this have to do with vaccines? Read on.

Last week, the Australian Government announced the national COVID-19 vaccine roll-out strategy. There are a lot of good things about the strategy, particularly the prioritisation of Aboriginal and Torres Strait Islander Australians – a population at high risk of developing severe COVID-19.

As part of the strategy, the Australian Government has entered into four separate agreements to obtain vaccines. These agreements give Australia access to 10 million doses of the Pfizer/BioNTech vaccine, 53.8 million doses of the University of Oxford/AstraZeneca vaccine, 51 million doses of the Novavax vaccine, and more than 25 million doses of these and other vaccines which become available through the COVAX Facility.

Two doses are required for vaccination, so the number of people who can be vaccinated with each vaccine will be about half of what the numbers suggest.

It sounds good, but there’s a problem. Phase 3 trials are not yet complete for the Novavax vaccine, so the Government intends to chiefly rely on two vaccines. People who are vaccinated in the first phase(s) will likely receive the Pfizer/BioNTech vaccine, and the rest of the population will receive the Oxford/AstraZeneca vaccine.

This matters, because the Oxford/AstraZeneca vaccine has a much lower efficacy than the Pfizer/BioNTech vaccine.

Efficacy of the Oxford/AstraZeneca vaccine is modest

The efficacy of the Oxford/AstraZeneca vaccine (defined as preventing symptomatic, test-confirmed COVID-19) is 62.1%.

However, although this vaccine is not able to completely prevent symptomatic infection in everyone, it might be reasonably effective at preventing severe COVID-19. No-one in the trial who received the vaccine was hospitalised, compared to 10 people in the placebo group.

In contrast, the efficacy of the Pfizer/BioNTech vaccine is 95.0%.

The results of the Pfizer/BioNTech trial aren’t a blip. Moderna designed a vaccine using the same mRNA technology as Pfizer/BioNTech. The Moderna vaccine was found to have an efficacy of 94.1%.

To put these results in context, the influenza vaccine typically reduces the risk of getting sick by about 40-60%.

How well these vaccines prevent any infection (not just symptomatic infection) is uncertain, but efficacy is likely below these figures. The Oxford/AstraZeneca trial has been the only one to assess this so far, and the results weren’t encouraging. When people were given a low dose of the vaccine initially, followed by a higher booster dose, the efficacy was 58.9%. But when people were given two standard doses, efficacy was only 3.8%. In other words, the Oxford/AstraZeneca vaccine can’t protect against infection completely with the standard dosing schedule.

If we gave the Oxford/AstraZeneca vaccine to the majority of Australians, a substantial proportion of the population won’t be protected from symptomatic infection, and Australia definitely won’t achieve herd immunity.

We won’t reach herd immunity with the Oxford/AstraZeneca vaccine

We can calculate the proportion of people who need to be vaccinated to achieve herd immunity with this simple formula:

    \[Coverage = {1 \over V_{e}} \times {(1 - {1 \over R_{0}})\]

    \[\mbox{Where } V_{e} \mbox{ is vaccine efficacy, and } R_{0} \mbox{ is at least 2.5 for SARS-CoV-2}\]

We can see that we’d probably need to vaccinate over 96% of the population to achieve herd immunity if we used the Oxford/AstraZeneca vaccine, but perhaps only 63% with the Pfizer/BioNTech vaccine.

Even in a perfect world where everyone was willing and able to be vaccinated, we wouldn’t be able to achieve herd immunity using the Oxford/AstraZeneca vaccine. That’s because children and adolescents make up about one-fifth of Australia’s population, and the vaccine is not yet authorised for use in this age group.

It gets worse, because we’re now facing variants of SARS-CoV-2 which are substantially more transmissible, and hence have a higher basic reproduction number (R0).

The emergence of the UK variant (B.1.1.7) has changed everything. It’s no longer possible to achieve herd immunity against it with the Oxford/AstraZeneca vaccine, although herd immunity can likely still be achieved with high efficacy vaccines such as the Pfizer/BioNTech or Moderna products.

A failure to achieve herd immunity would mean Australia would be dealing with outbreaks for years to come.

Weighing up the options

This isn’t to say that the Oxford/AstraZeneca doesn’t have some advantages. It does. It can be manufactured in Australia (unlike the Pfizer/BioNTech vaccine), is much cheaper (about $3.25 per dose, compared to $26), and can be stored at fridge temperature (unlike the Pfizer/BioNTech vaccine, which must be stored below minus 70 degrees Celsius).

But Australia has other options. The Novavax vaccine can also be manufactured domestically, and like the Oxford/AstraZeneca vaccine, it only requires refrigeration at 4 to 8 degrees Celsius.

More importantly, preliminary results from an Australian trial showed people who received the Novavax vaccine developed very high antibody levels – about four times higher than patients who had recovered from COVID-19.

Additionally, animal studies suggest the Novavax vaccine is more likely to confer the much-prized sterilising immunity compared to other vaccines. This means that a vaccinated person is both unlikely to get sick and won’t transmit the virus either.

It has some other advantages, too. It’s been tested with a very wide range of people from diverse ethnic backgrounds, as well as people living with chronic health issues, including HIV. Trials of the vaccine are currently being conducted in the UK and South Africa, which will let us see how well the vaccine performs against some of the new and concerning variants.

Novavax may end up being the vaccine that ticks all the boxes for Australia. If it delivers sterilising immunity, it could end COVID-19 in Australia for good, and that’s the long-term goal we should seek.

Interim results from the UK phase 3 trial will likely be released in the next few weeks.

A fork in the road

Professor Raina MacIntyre, one of Australia’s leading epidemiologists and head of the Biosecurity Program at the Kirby Institute, warned against short-term thinking in a recent interview:

 “It’s like a fork in the road – whichever choice we make will take us one way or another. Either into a situation where we’re living with COVID forever, or a situation in which we can actually achieve elimination of COVID in Australia.”

Professor Raina MacIntyre

So what should Australia do? Our immediate goal should be to secure our borders to prevent COVID-19 from entering Australia. The high efficacy Pfizer/BioNTech vaccine should be used to do this, by vaccinating workers at ports, airports, and the hotel quarantine system, along with frontline healthcare workers.

Aged care staff and residents must be promptly vaccinated, too.

The Government should also try to procure the high efficacy Moderna vaccine, and use this in preference to the Oxford/AstraZeneca vaccine.

If the Novavax trial is successful and demonstrates high efficacy, the Government should immediately engage CSL to produce the vaccine in Australia, and then use the Novavax vaccine to vaccinate the remainder of the population.

Final words

To be clear, there are no concerns regarding the safety of the Oxford/AstraZeneca vaccine. If it were Australia’s only option, I would be comfortable being vaccinated with it.

I would also recommend widespread use of the Oxford/AstraZeneca vaccine if the epidemiological situation were more serious. If Australia were faced with high levels of community transmission like those seen in the UK, then the priority should simply be to get vaccines into arms. The Oxford/AstraZeneca vaccine clearly will save lives.

But the situation in Australia is very different. We do not have an immediate epidemic to fight. Our focus must be the long-term protection of Australia.

For that, we need herd immunity, and to achieve it, let’s pick the Toyota of vaccines, not the Holden Camira.

9 replies on “Australia needs herd immunity”

I have a question. When you calculate coverage, why do you use the efficiencies for preventing symptomatic infection? A substantial portion under the coverage could still get infected (asymptomatic) and pass the disease on. So therefore, why would the disease disappear? In other words, for coverage, wouldn’t you want to use efficiencies for preventing all infections (sterilizing immunity)? That way, no one could pass the disease along. I hope this question makes sense. Please tell me where I’m going wrong. Thank you!

You’re right to say that the efficacy for any infection is the one that should be used in the herd immunity calculation. This is 58.9% – at best – for the Oxford vaccine, and unknown for the mRNA vaccines.

It will be less than the figures quoted for symptomatic infection, but by how much is anyone’s guess.

However, there may be some wiggle room in the numbers, because it appears that people with symptomatic COVID-19 are more likely to transmit the virus than people who are completely asymptomatic.

So even if efficacy turns out to be quite a bit lower than the initial impressive figures for the mRNA vaccines, herd immunity might still be achievable by virtue of having fewer symptomatic infections.

Time (and more data) will tell.

One of the things no one seems to explain is why we can’t vaccinate someone with AZ 1st and then re-vaccinate them with a higher efficiency vaccine later.

Presumably there is a reason, but what is it?

The short answer is that it’s untested. It might be possible to do what you’ve described, and it might even result in better protection than using either vaccine alone. See: https://www.nationalgeographic.com/science/2020/12/should-you-take-more-than-one-type-coronavirus-vaccine-to-boost-immunity/

However, there’s a theoretical possibility (albeit unlikely) that combining different vaccines could lead to a more serious course of illness after infection. This phenomenon is known as vaccine-induced enhancement. It probably won’t happen, but we need to thoroughly evaluate the safety of this approach before it’s tried.

Thank you for such a clear explanation. Living in the U.K. and being in priority 3 I was concerned about having the right vaccine. Just from the data I’d have chosen Pfizer but then was concerned about delaying the second dose. I won’t get a choice but reassured that with the situation as it is here after reading this article will be happy to have whatever is offered.

Thanks, Chris. Rest assured that any of the vaccines are appropriate for the situation in the UK and will save lives.

It seems to me that the mRNA vaccines while having great efficiency might not be as efficient with some variants (E484K for example). If that’s indeed the case (not enough data now) even these vaccines won’t make it possible to achieve herd immunity…

The efficacy standard was different for the different trials. AstraZeneca had a more strict definition of effective. You can’t compare the stats when they’re using different objectives. The other vaccines could be just as successful when/if tested properly.

That’s not correct. The definition was not more strict in the Oxford trial.

Here are the primary endpoints:

Oxford/AstraZeneca:
“The primary outcome was virologically confirmed, symptomatic COVID-19, defined as a NAAT-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia).”

Pfizer/BioNTech:
“The first primary end point was the efficacy of BNT162b2 against confirmed Covid-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose … Confirmed Covid-19 was defined according to the Food and Drug Administration (FDA) criteria as the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting, combined with a respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification–based testing, either at the central laboratory or at a local testing facility (using a protocol-defined acceptable test).”

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