Moderna’s experimental Omicron booster generates high levels of antibodies that neutralize subvariants BA.4 and BA.5, according to preliminary clinical trial data.
- Omicron subvariants BA.4 and BA.5 are becoming the dominant forms of COVID-19 in Australia and abroad
- New data from Moderna shows an updated booster tailored to Omicron generates high levels of antibodies against BA.4 and BA.5
- Moderna’s chief medical officer says, pending approval, the new booster could be supplied to Australia in August
These subvariants have gained a foothold in the US and Australia, and are already driving a new wave of infections in the UK.
Moderna’s results, which have not been peer-reviewed, build on an announcement earlier this month that people given the new booster made more Omicron-fighting antibodies in general than if they got a fourth dose of the original vaccine.
Paul Burton, Moderna’s chief medical officer, said trial participants’ antibody levels were high enough to provide “good clinical protection” against BA.4 and BA.5.
“We know that an antibody level of about 400 units … provides very good clinical protection against COVID infection, and certainly against more severe disease, hospitalization and death,” he said.
Of the 437 adults who had the Omicron-specific booster, those who hadn’t yet had COVID generated average BA.4- and BA.5-neutralising-antibody levels of 727 units after a month.
People who had a prior COVID infection saw a massive jump in BA.4- and BA.5-neutralizing antibodies: more than 2,700 units.
Participants are being tracked to see if they do, eventually, catch COVID, and when.
University of Queensland infectious diseases physician and clinical microbiologist Paul Griffin said neutralizing antibody responses were a good surrogate for protection, but seeing how well the booster worked in the real world was most important.
“Obviously, that takes more time to accumulate that data, so this is a useful first step, but then clinical studies will follow that will hopefully show efficacy in people.”
A two-in-one COVID shot
The updated Moderna booster, called mRNA-1273.214, was developed in January, when Omicron was sweeping Australia.
The shot contains instructions in the form of mRNA for your body to construct spike proteins — protrusions the virus uses to infect our cells.
Your immune system then makes antibodies against various parts of the spike protein. Should those antibodies encounter spike proteins again in the form of the real virus, they will recognize and grab hold of it.
And if they clamp on the end of the spike, which is the part that latches onto our cells, they neutralize it.
But if the spike protein changes too much, especially its grabbing end, this neutralizing power drops.
To get around this, the new Moderna booster has mRNA instructions for the spike protein from two viruses: the ancestral SARS-CoV-2 virus that originated in Wuhan, plus the Omicron subvariant BA.1, which was circulating in January.
In the months since, other Omicron subvariants spun off, with BA.4 and BA.5 now starting to dominate new infections in many parts of the world.
BA.4 and BA.5 have the same raft of genetic mutations in their spike protein, slightly changing its shape, and allowing it to slip under the immune system’s radar and evade some of the antibodies we might have made against other variants — including antibodies produced during BA.1 infection.
So how can a vaccine against two viruses — the original and Omicron BA.1 — make antibodies that neutralize a whole heap of others?
This is a phenomenon called “epitope broadening”, Dr Burton said, something Moderna saw in trials of another variant-specific booster that included mRNA for the ancestral virus and Beta variants.
“When you bring two mRNAs together, and two slightly different versions of the spike protein are then produced in your body … you don’t just get antibodies against what you’re putting in. You get this very broad cover of all sorts of potential new variants.
“If you now have Wuhan and Omicron, which is so far away from the original Wuhan, and you bring them together [in an mRNA vaccine]you can get very high levels of antibody produced against BA.1, BA.2, BA.4 and 5, plus Delta and Beta and everything else.”
This, according to RMIT University professor of immunology Magdalena Plebanski, is “the really good news.”
Omicron’s not the last COVID variant, and previous variants might crop up again down the track.
“[The booster] is not just tackling a new strain, and then losing potency against the previous strains,” Professor Plebanski said.
For the US and European autumn … and Aussie winter?
Moderna is submitting clinical trial data to an academic journal and angling to deploy the updated booster for the northern hemisphere’s autumn.
By then, BA.4 and BA.5 “will probably be a distant memory”, but the new booster will cover variants that are yet to rear their head, Dr Burton said.
“Our aim as well though is to be able to support Australia and its winter and try, with TGA and ATAGI endorsement, to provide this candidate vaccine booster to Australia, even in August.”
The updated Moderna shot is a reasonable booster choice, Professor Plebanski said.
“And time is of the essence. At some point, our immunity [generated from third or fourth doses of COVID vaccine] will wane.”
Dr. Griffin agreed. Variant-specific boosters are the way forward, he said, and they’ll be adjusted as needed, like the seasonal flu vaccine.
“But it’s not going to be as straightforward as some people might think right now, though, because we really have to think about the best time to use [a booster],” he said.
The messaging around why variant-specific boosters are needed will also have to be thoughtfully considered to ensure sufficient and timely booster uptake, Dr Griffin added.
“It’s all well and good to develop this, but if we don’t roll it out quickly, it may be redundant.
“And if the uptake is not high enough, it’s not going to have the impact we need.”