Targeting epitopes to improve vaccines

Obtaining a vaccine that works against COVID-19 has been one of the main priorities of recent times. Numerous candidate vaccines, using different technological platforms, have been developed. These vaccines, designed by expressing the SARS-CoV-2 spike surface protein, induce neutralising antibodies against this virus.

However, the emergence of variants such as Alpha or Delta, that have increased transmissibility and are able to partially escape antibodies induced by previous infection or by vaccination, means that the vaccines need to be updated. In addition, other viruses of the same genus, the sarbecoviruses, have been responsible for epidemics over the last 20 years (SARS-CoV-1 and MERS-CoV). A future pandemic in the coming years caused by a coronavirus cannot therefore be excluded. It is therefore essential to develop an effective vaccine not only against SARS-CoV-2 variants, but also against other coronaviruses.

American researchers (at the Massachusetts Institute of Technology and Harvard) have identified highly conserved regions of SARS-CoV-2 amongst the variants and sarbecoviruses, so as to identify epitopes (regions targeted by immune defences) that may serve in the design of new vaccines effective against variants and other coronaviruses.

The researchers firstly analysed the protein structure of SARS-CoV-2 to define highly conserved regions between variants and other sarbecoviruses. After identifying regions of interest in the virus proteins, they defined epitopes for CD8 T-cells using predictive bioinformatic analysis. In addition to neutralising antibodies, CD8 T-cells are an essential component of an effective vaccine. They enable the destruction of infected cells and the building of long-term immune-memory. In addition, unlike neutralising antibodies that target only the spike surface protein, the CD8 T-cells can target other virus proteins, notably the most conserved regions between sarbecoviruses.

The scientists then showed that the epitopes defined by bioinformatic analysis are recognised by CD8 T-cells arising from SARS-CoV-2 infection. The CD8 T-cells tested came from 20 healthy donors and 30 patients who had been infected by SARS-CoV-2.

The researchers then redid the same tests, but using CD8 T-cells induced by a COVID-19 vaccine. The CD8 T-cells were taken this time from individuals having received 2 doses of vaccines based on mRNA technology: 13 people had had the Pfizer-BioNTech vaccine and 10 people the Moderna vaccine. However, the CD8 T-cells from vaccinated individuals recognised the identified epitopes less well than the CD8 T-cells from individuals who had been infected with SARS-CoV-2.

The scientists were able to define epitopes (targets of the CD8 T-cells) in 15 regions of viral proteins conserved between SARS-CoV-2 and other sarbecoviruses. These epitopes may therefore be ideal targets in the design of a vaccine based on a large-scale CD8 T-cell reaction, effective against SARS-CoV-2, but also against other coronaviruses of the same genus. These results show that there is a possibility of updating vaccines to make them more effective against variants.