How to adapt an mRNA vaccine to virus variants

Interview with NRP 78 researcher Steve Pascolo of the Zurich University Hospital. He and his team are focusing on optimising mRNA vaccines.

How is an mRNA vaccine adapted to new virus variants? 

So far, no adaptation of the mRNA vaccines has been needed as the mRNA vaccines (Moderna and BioNTech/Pfizer) provide good protection against all variants. If a variant evades the immunity induced by those two vaccines, new mRNA vaccines will be generated that contain mRNA coding for the variant spike (possibly combined 50-50 with mRNA coding for the Wuhan spike contained in the existing vaccines). Moderna is in phase II for vaccines specific to the Beta and Delta variants. BioNTech is likely to have Beta, Delta and Omicron mRNA vaccines ready in the laboratory and could probably proceed to the clinical study phase quickly, if it is proven that the current vaccines do not protect against the Omicron variant.

How fast can this happen? 

To produce the new mRNA vaccines, it takes approximately two weeks to obtain the DNA that is used as a matrix to generate RNA in vitro, one week to generate the mRNA and two weeks to certify the batches. Thus it takes five to six weeks altogether to produce the new vaccine.

How long does it take to produce a new vaccine?

The companies anticipate variants and may already have the suitable variant-coding DNAs. Should the DNA already be "in the drawers", it could take only three weeks to produce the new vaccine. Production capacity is limited, however, so the production and distribution of millions of doses will take a few more weeks. And the production and distribution of doses for the whole world will of course need even more time.

What is the approval process for an adapted vaccine?

The authorities will decide whether they again need phase I, II and III data with the new mRNA sequence (coding for the variant spike) that would be used for the vaccine or whether, as is the case with flu vaccines, they will just approve a new vaccine with a different mRNA sequence that is adapted to variants. Furthermore, different agencies (FDA, EMA, Swissmedic) may take different decisions on this point.

Will booster vaccines be administered on a seasonal schedule in the future, similar to the flu vaccine, and adapted to the prevailing virus variants each time?

It is probable that anti-COVID vaccines will be given at least to vulnerable people every year together with the traditional flu vaccine. Later, new synthetic mRNA flu vaccines (in development by Moderna and BioNTech) could be combined with synthetic mRNA Covid vaccines so that several mRNA molecules (coding the relevant flu and SARS-CoV-2 proteins) are delivered in one shot, thus inducing immunity against both pathogens in one go before winter.

Project: An optimized mRNA vaccine against COVID-19