What's the difference in protection against Omicron between 2 doses and 3 doses of vaccine?

Australian Health Minister Greg Hunt said last week^[1] he expects the Australian Technical Advisory Group on Immunisation (ATAGI) to change the definition of “fully vaccinated” to three doses instead of two.

It comes as evidence emerges suggesting the highly infectious Omicron variant has the ability to escape the protection two vaccine doses offer.

So, how effective are two doses compared to three against Omicron?

Let’s break it down.

Two doses don’t protect much against Omicron

Vaccine protection against Omicron is reduced for two reasons.

First, antibodies generated by vaccination gradually wane^[2] over time. There are now many countries that are more than a year into their COVID vaccine rollout, so many people have received their second COVID jab over six months ago.

Without boosting, their antibody levels will have dropped significantly. Australia was a little slower off the mark – but now finds itself in a similar situation.

The second reason is Omicron can escape vaccine-induced immunity because of its constellation of mutations. Its spike protein (the bit that helps the virus access our cells) is significantly different to Delta’s, and to the original virus from which our vaccines are based.

The critical part of the spike protein is the “receptor binding domain”. It latches onto a protein on our cells called ACE-2 so the virus can gain entry. Delta had two mutations in the receptor binding domain, and Beta had three. Omicron has 15 mutations^[3] in its receptor binding domain. As a result, only some of the antibodies the vaccine induces will still bind to Omicron’s spike and inhibit it getting into your cells.

For these reasons, emerging evidence suggests two doses of a COVID vaccine provide just 0-10% protection against infection with Omicron^[4] five to six months after the second jab.

So, you really cannot claim you are “fully vaccinated” with just two doses now, particularly if it’s been months since your second dose.

Some protection against severe disease and hospitalisation remains. UK data suggests two doses of AstraZeneca or Pfizer offer around 35% protection against hospitalisation^[5] by six months after the second dose.

What about three doses?

Having a booster dose bumps up your antibodies – which is particularly important for Omicron because only some of those antibodies are protective. Emerging evidence suggests protection from symptomatic Omicron infection is restored to 60-75%^[6] two to four weeks after a Pfizer or Moderna booster dose.

However, third-dose protection also wanes, down to 30-40% against Omicron infection^[7] after 15 weeks.

So, unfortunately breakthrough infections will still be common. Fortunately, protection against hospitalisation remains much higher, up around 90% after a Pfizer booster dose and only dropping to 75% after 10-14 weeks^[8], and 90-95% up to nine weeks after a Moderna booster.

Pfizer^[9] and Moderna^[10] are currently developing vaccines matched to Omicron, which if approved, should induce better immunity against this variant.

Read more: Will an Omicron-specific vaccine help control COVID? There's one key problem^[11]

Will we need a new dose every three months?

Israel is currently rolling out fourth Pfizer doses^[12] to some high-risk groups.

Some people will be concerned this trend means we’ll need a new dose every few months. But I don’t think that will be the case.

We can’t keep boosting people every few months chasing waning immunity. It’s likely after each round of boosting, faith in the vaccines will diminish. It’s worth remembering we have never tried to vaccinate against a respiratory coronavirus so we are still learning about how to best generate protective immunity.

There’s also the ethical question of rolling out multiple rounds of booster doses in wealthy countries when many people in some parts of the world haven’t received their first two doses yet.

While there are high levels of infection in countries with low rates of vaccination, all countries remain at risk of outbreaks, particularly if new viral variants emerge – which is sure to happen while there’s so much transmission globally.

Read more: Israel is rolling out fourth doses of COVID vaccines. Should Australia do the same?^[13]

But better vaccines are coming. Universal COVID vaccines are in development^[14], which target areas of the virus that don’t easily mutate, meaning they’ll likely be effective across different variants.

In the future, we may get a yearly COVID vaccine combined with the flu vaccine. Treatments will improve, too, so you can minimise symptoms at home.

These developments will reduce the impact the virus has on us, so eventually COVID will stabilise to a predictable level of transmission that doesn’t cause disruption – that is, it becomes endemic.

Your existing immunity will be boosted with naturally acquired infections every year or so that will almost always be asymptomatic or very low (cold-like) symptoms.

However, for those more vulnerable, such as the elderly and those who are immune compromised or have chronic diseases, vaccines are less effective and the virus will still be able to cause severe illness and death, similar to the flu. So we need to continue to progress research into new treatment approaches that will better protect these individuals.

A silver lining

One silver lining from COVID has been intensified research efforts towards vaccines and treatments.

We’re seeing multiple new anti-viral drugs being approved which will reduce disease and death.

Some of these treatments are likely to be effective across different viruses, not just COVID.

And mRNA vaccine technology can churn out new vaccines in a matter of months, which was completely inconceivable two years ago.

All this means we’re better prepared against COVID, but also future respiratory virus outbreaks and pandemics, whether that’s a new coronavirus, influenza virus or any of the multitude of other respiratory viruses out there.

References

1. ^{^} said last week (www.skynews.com.au)
2. ^{^} gradually wane (media.nature.com)
3. ^{^} 15 mutations (www.nature.com)
4. ^{^} 0-10% protection against infection with Omicron (assets.publishing.service.gov.uk)
5. ^{^} around 35% protection against hospitalisation (assets.publishing.service.gov.uk)
6. ^{^} restored to 60-75% (assets.publishing.service.gov.uk)
7. ^{^} 30-40% against Omicron infection (assets.publishing.service.gov.uk)
8. ^{^} dropping to 75% after 10-14 weeks (assets.publishing.service.gov.uk)
9. ^{^} Pfizer (www.cnbc.com)
10. ^{^} Moderna (www.reuters.com)
11. ^{^} Will an Omicron-specific vaccine help control COVID? There's one key problem (theconversation.com)
12. ^{^} fourth Pfizer doses (www.thelancet.com)
13. ^{^} Israel is rolling out fourth doses of COVID vaccines. Should Australia do the same? (theconversation.com)
14. ^{^} are in development (www.nejm.org)