Coronavirus: Second-generation mRNA vaccine appears safe, could work against all variants

A new COVID-19 vaccine using second-generation mRNA technology appears to stimulate an immune response equivalent to the existing vaccines, but at only a fraction of the dose. Photo credit: Getty Images

A new COVID-19 vaccine using second-generation mRNA technology appears to stimulate an immune response equivalent to the existing vaccines, but at only a fraction of the dose.

After decades of research, the world's first mRNA vaccines were rushed into production in 2020 to combat the COVID-19 pandemic. The efficacy of the Moderna and Pfizer/BioNTech vaccines against infection with the virus' original strain - above 90 percent - stunned scientists, far surpassing the 50 percent threshold US health authorities set for approval. 

But an unequal rollout of the vaccines - mRNA and traditional - has left some parts of the world with minimal protection, giving the virus the chance to evolve mutations. The Omicron variant in particular appears to ignore protection offered by the standard two-dose immunisation, prompting highly vaccinated countries to start offering booster doses. 

The problem is the existing mRNA vaccines work by showing our immune system what the SARS-CoV-2's virus' spike protein looks like - as the name of Moderna's vaccine, Spikevax, makes clear. But most of the virus' mutations to date have been happening on the spike protein - allowing variants to slip through our first line of defence, unrecognised.

A new vaccine, intended at this stage to be used as a booster, hopes to fix that. US biotech company Gritstone Bio and the University of Manchester have teamed up to create a second-generation mRNA vaccine that "delivers antigens from both spike and non-spike proteins".

"As we have seen with the Omicron variant, viral surface proteins such as spike are mutating at a high rate, leaving the immunity provided by spike-dedicated vaccines vulnerable to variants containing numerous Spike mutations," said Andrew Allen, Gritstone chief executive. 

The current Pfizer/BioNTech and Moderna vaccines use non-amplifying mRNA, while the new one uses self-amplifying mRNA (saRNA) - like mRNA, saRNA gets the body's cells to produce parts of the virus so the immune system can learn to recognise it. But saRNA is able to amplify the process, producing far more antibodies than mRNA at the same dose. 

The existing vaccines use between 30 and 100 micrograms of mRNA - Gritstone's saRNA vaccine uses just 10 micrograms. 

In a trial involving a small number of volunteers, the saRNA booster was given to people who'd already had two doses of the non-mRNA AstraZeneca vaccine. No serious side effects were found and a strong T cell response was triggered, which can help fight off any variants regardless of their spike protein mutations. 

The researchers next plan to expand the trial from 20 to 120.

"It is increasingly apparent that a focus on T cell immunity is an important way to generate the robust and durable immunity that may prevent future SARS-CoV-2 variants from causing severe disease, hospitalisation, and death," said Andrew Ustianowski, honorary clinical chair at the University of Manchester. 

"We know the immune response to first generation vaccines can wane, particularly in older people. Coupled with the prevalence of emerging variants, there is a clear need for continued vigilance to keep COVID-19 at bay.

"We believe this vaccine, as a booster, will elicit strong, durable, and broad immune responses, which may well be likely to be critical in maintaining protection of this vulnerable elderly population who are particularly at risk of hospitalisation and death."

Even though the first-generation vaccines have shown waning efficacy against infection against variants, they still appear to be very effective at preventing hospitalisation and death.