The first combination COVID booster has now been introduced to Australia's vaccine program, with Moderna's Omicron shot officially entering the rollout from today, according to the Department of Health and Aged Care.
The Australian Technical Advisory Group on Immunisation (ATAGI) last month recommended the shot, comprising of vaccines against the original SARS-CoV-2 virus and the BA.1 Omicron subvariant, be administered as a booster to adults.
Combination boosters have also been rolled out elsewhere, such as the UK, Switzerland, Canada, EU and US, with the US rolling out a booster tailored to BA.4 and BA.5 rather than BA.1.
So who can get the new booster, and how much protection does it provide?
Who can get it, and how?
Moderna's new booster, called Spikevax Bivalent Original/Omicron, or mRNA-1273.214, has been approved for use in people aged 18 years and over.
ATAGI recommends it be administered at least three months after your most recent COVID‑19 vaccine dose or COVID infection — but you don't need to get it if you're already up-to-date with your boosters (ATAGI's recommended number of vaccine doses — four for most people, five if you're immunocompromised — hasn't changed).
The combination booster can be administered at the same time as non-COVID vaccines.
It's not yet been approved for under-18s, nor is it to be used as a "primary dose" vaccine (one of the first two doses in most people or first three doses in severely immunocompromised people).
To find out where the new boosters are available, you can use the health department's clinic finder.
How is the new booster different from the original Moderna COVID vaccine?
Like the original Moderna COVID primary and booster shots, the combination booster is an mRNA vaccine.
It contains genetic blueprints that, when injected into our muscle, prompt our body to construct replicas of the SARS-CoV-2 spike protein.
These alert our immune system, which produces antibodies that form an immune "memory" of the spike. They can then neutralise the real virus, should the immune system encounter it down the track.
But where the first Moderna vaccine only contained spike protein blueprints for the original SARS-CoV-2 virus, the new combination booster also includes blueprints for the Omicron BA.1 subvariant spike, which was circulating widely when the vaccine was developed earlier this year.
BA.1 — and its suite of Omicron siblings — have at least 30 mutations in their spike protein compared to the original virus, giving their spikes a slightly different shape.
The original COVID vaccines are less effective at neutralising infections caused by these new subvariants, as the antibodies they generated are less likely to recognise Omicron spike proteins (but some still can).
Why include mRNA for the original virus at all?
Given almost none of the ancestral SARS-CoV-2 virus is circulating now, and Omicron has dominated infections in 2022, why include mRNA against the original virus at all?
When faced with less-mutated variants such as Delta, original mRNA vaccines provide strong protection against infection, hospitalisation and death (although this waned over time).
And we don't know what the virus will do next.
It will almost certainly spin off into another variant, but older ones might make a comeback, so having broader protection is a way of pre-empting future potential infections.
How well does it work?
Pretty much everything we know about Moderna's combination boosters comes from Moderna's own trials.
Preliminary results showed what ATAGI called "a small incremental benefit" in an immune response against Omicron subvariants BA.1, BA.4 and BA.5.
In a study published in the New England Journal of Medicine, around 800 triple-vaccinated people received either a fourth dose of the original Moderna vaccine or the new combination booster.
Both cohorts made antibodies that could neutralise the ancestral virus and BA.1 — they're similar enough for the original vaccine to generate some antibodies capable of latching onto BA.1 — but those who had the combination booster ended up with an average 1.75 times the BA.1 antibody response after 28 days when compared to the original vaccine group.
The combination shot also gave recipients higher antibody levels against the BA.4 and BA.5 variants, especially if they'd been infected with COVID previously.
Moderna's chief medical officer Paul Burton told the ABC in June that these antibody levels are "guaranteed to correlate with clinical protection against infection and against severe disease".
But precisely how such antibody levels translate to preventing infection, hospitalisation and death in the real world isn't known yet, nor do we know how long the antibodies last.
There were some breakthrough infections in Moderna's study.
The researchers wrote, "in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the [combination] booster and in nine participants after the [original] booster".
Of those, six and seven respectively were asymptomatic infections.
It's also important to note that we already know the original Moderna vaccine provides protection against severe disease against Omicron subvariants, and ATAGI recommends "people who are due for a COVID-19 dose book an appointment, using whichever vaccine is available to them".
How safe is the new booster?
Moderna's combination booster has a similar safety profile to the original.
In trials, the most commonly reported local adverse reactions following the combination shot as a fourth COVID vaccine dose, or second booster, were pain at the injection site (77 per cent), fatigue (55 per cent), headache (44 per cent) and muscle aches (40 per cent).
Moderna's combination booster trial is ongoing, and in a media release, the TGA confirmed the pharmaceutical giant must provide information about longer-term results from such studies — including safety assessments — as well as continued monitoring after the vaccine's rollout.
Like previous COVID vaccines, combination boosters will be batch-tested before being distributed to and administered at participating pharmacies and medical clinics as part of the existing rollout.
What other variant-specific vaccines are coming down the line?
Moderna's combination shot might be the first to be used in Australia, but it won't be the last.
Pfizer and Novavax are trialling vaccines that aim to protect against more than one variant.
Research is also underway into slimmed-down versions of current COVID vaccines, which are designed to try to generate a higher proportion of neutralising antibodies, as well as vaccines that target parts of the virus that don't mutate as quickly as the spike protein.
