Covid: Developing 2 new vaccines that improve efficacy

Developed by a team of researchers two new candidates for the vaccine against covid-19 which in the preclinical phase have shown to increase immunogen production compared to vaccines of the same type already on the market.

The research, published in the scientific journal Nature Communications, was led by IrsiCaixa – a center jointly promoted by the “la Caixa” Foundation and the Department of Health of the Generalitat of Catalonia (Northeast) -, Animal Health Research Center of the Institute of Agricultural-Food Research and Technology (IRTA-CReSA) and the Barcelona Supercomputing Center – National Supercomputing Center (BSC-CNS), with funding from Grifols.

The vaccines are based on two mutated versions of the spike protein or S protein of SARS-CoV-2, called S29 and V987H, which increase the production of this protein up to five times compared to other vaccines on the market.

Most of the vaccines against covid-19 put on the market so far are based on protein S for two reasons: it is an essential part of the infection process and activates the immune system against the virus.

Despite these advantages, protein S also presents a challenge, since it is not stable and changes conformation.

This complicates its production and implies that certain conformations hide the region of the protein – called the RBD – with the greatest capacity to activate the immune system.

Therefore, most vaccines targeting this compound—such as those from Pfizer/BioNTech, Moderna, AstraZeneca, and Janssen—stabilize the S protein by incorporating two mutations, leading to a variant called 2P.

Despite efforts so far, the protein is still produced at low levels, so scientists consider it necessary to find alternative mutations that increase its production.

Using supercomputer techniques, the team identified various mutations that favor its stability.

“We used computational tools to predict which mutations manage to reduce its mobility and we chose those that offered us a more stable version of the S protein with better exposure of the RBD domain,” said Víctor, a BSC-CNS researcher. Gualar.

From these mutations, the team generated two new S protein variants, S-29 and S-V987H, which were shown to achieve improve production compared to current vaccines protein S.

“We multiplied the level of protein production in the laboratory two to five times,” said Carlos Ávila, a researcher at IrsiCaix.

Contribution to the future generation of vaccines
Therefore, the researchers propose the use of these new variants of the S protein in the next generation of vaccines that use the spike protein to activate the immune system.

“We saw that in a model of severe disease, vaccines protect against progression to severe infection and that they reduce the amount of virus present in tissues in a model of moderate disease,” said IRTA-CReSA researcher Júlia Vergara-Alert.

They are also proven to be effective against omicron, beta and D614G variants of SARS-CoV-2.

Despite the great impact of the Covid-19 vaccine in controlling the pandemic, SARS-CoV-2 is still present and, as it infects and transmits, it also adopts new mutations that give it useful capabilities, such as better transmissibility or evasion of the immune response.

Therefore, the scientific community continues to work to develop vaccines that adapt to these new capabilities of SARS-CoV-2.