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Moderna’s improved mRNA covid-19 vaccine is effective at lower doses


Moderna’s original RNA vaccine for covid-19 was first rolled out in 2021

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Moderna has created a streamlined version of its mRNA vaccine against covid-19 that is effective at lower doses and lasts twice as long when stored in a refrigerator. The vaccine includes only two key parts of the spike protein of the virus, instead of the entire protein.

The improved vaccine, called mRNA-1283, has “demonstrated encouraging results in multiple clinical studies” and the company has now completed enrollment of its late-stage clinical trial, Moderna announced on 13 September.

Numerous studies have shown that the most effective antibodies against the SARS-CoV-2 coronavirus bind to one of two key sites on the spike protein that protrudes from the virus’s surface. One of these sites, for instance, is the part of the protein that attaches to human cells and helps the virus get inside, so antibodies that bind to this site block this process.

However, almost all existing covid-19 vaccines consist of the entire spike protein, prompting the immune system to generate antibodies against other parts of the protein, many of which aren’t effective.

So, Moderna has created a vaccine that consists of an mRNA coding for just the two parts of the protein containing the key sites. Animal tests showed that linking these two parts produced a better response than when they were separate, according to a paper in Science Translational Medicine, also released on 13 September.

The first human trial of this vaccine revealed that even people given a tenth of what is the standard dose for Moderna’s existing covid-19 vaccine, called mRNA-1273, produced an antibody response that was just as strong as a full dose of the original vaccine, according to a preprint released in October 2022.

Consequently, the company selected lower doses for subsequent clinical studies, says Darin Edwards, who leads Moderna’s covid-19 vaccine programme. The results of the phase 2 studies haven’t yet been released.

Because the mRNAs in mRNA-1283 are shorter than those in mRNA vaccines coding for the entire spike protein, they are less likely to break up, giving the vaccine a longer shelf life. When stored between 2°C and 8°C (36°F and 46°F), it takes a year for 40 per cent of the mRNAs to degrade in mRNA-1283, compared with six months for mRNA-1273.

The version of mRNA-1283 being tested in the latest trial is a two-part vaccine, with half the mRNAs coding for the key sites from the original SARS-CoV-2 virus and half for the BA.4 and BA.5 omicron subvariants, says Edwards. It will be updated to target newer variants if and when it receives regulatory approval.

The latest mRNA booster shots now being rolled out target the XBB.1.5 omicron subvariant that replaced BA.4 and BA.5. They no longer contain the original virus, after studies suggested that including it weakened the immune response.

The US approved the XBB.1.5-based booster vaccines made by both Moderna and Pfizer/BioNTech on 11 September, while the UK approved the Pfizer/BioNTech one on 5 September. However, many people getting boosters in the UK are likely to be given stockpiled vaccines targeting older variants.

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