Data requirements in place in the EU for second-generation COVID-19 vaccines

26 February 2021

With continued mutations of SARS-CoV-2, the current COVID-19 vaccines may need to be adapted to ensure their efficacy. To ensure that second-generation vaccines can be made available as fast as possible, the European Medicines Agency has just issued guidance for manufacturers.

There are presently three COVID-19 vaccines authorised in the EU: BioNTech/Pfizers Comirnaty, COVID-19 Vaccine Moderna and COVID-19 Vaccine AstraZeneca. Phase 3 clinical trials with thousands of trial subjects have established that all three vaccines offer protection against COVID-19 evidenced by fewer disease cases. In addition, the test results indicate that people who get the disease despite being vaccinated have a milder disease course than those who have not been vaccinated.

It is a well-known fact that viruses mutate. This is also the case for SARS-CoV-2 and COVID-19. The current COVID-19 vaccines provide protection against the virus variants that are most prevalent in Europe. However, the authorised vaccines may need to be adapted to provide continued protection against any variants of SARS-CoV-2.

To ensure that second-generation vaccines can be made available as fast as possible, the European Medicines Agency, EMA, has just issued guidance for vaccine manufacturers.

Small-scale clinical trials required to provide data on the efficacy of second-generation vaccines

The guidance describes the data required for the authorisation of second-generation vaccines.

The guidance assumes that the second-generation vaccines will rely on the same technology and platform of the original vaccines. The difference would be the specific antigen used in the vaccine to trigger the intended immune response in the body, which is what prepares the immune system to recognise and defend itself against the disease in case of infection.

Thus, the manufacturers will not be required to conduct the same large-scale phase 3 clinical trials that were conducted prior to the authorisation of the current vaccines.

The efficacy of second-generation vaccines for COVID-19 may instead be established in small-scale clinical trials with a small group of trial subjects who have not been vaccinated or infected with SARS-CoV-2. The clinical trials should be randomized to strengthen the reliability of the results. This means that the trial subjects will be randomly allocated in two equal-sized groups to receive either the original vaccine or the second-generation vaccine.

The study is to establish if the second-generation vaccine can trigger as many antibodies against the SARS-CoV-2 variant as the original vaccine did against the original SARS-CoV virus.

For the vaccine to be authorised fast, it must be manufactured in the same way as the original vaccine. The only difference allowed is the change of antigen to match the SARS-CoV-2 variants that the vaccine intends to offer protection against. If the manufacturing process for the vaccine is changed significantly, then the vaccine would need to be authorised from the beginning.

If a second-generation vaccine is to offer protection against several different SARS-CoV-2 variants with multiple antigens included in the vaccine, it is likely that additional evidence will be required.

A process resembling that of seasonal influenza vaccines

The adjusted requirements for COVID-19 second-generation vaccines are similar to those applicable to influenza vaccines. The virus strains of seasonal influenza vaccines are changed almost every year to offer protection against those influenza virus variants that are present in the community. 

Further reading: Adapting COVID-19 vaccines to SARS-CoV-2 variants: guidance for vaccine manufacturers.


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