Next-Generation Vaccine Strategy Proposed for SARS-CoV-2

A study led by the Garvan Institute of Medical Research has revealed a guide to developing COVID-19 vaccines that both prevent the coronavirus from infecting human cells and that are more resistant to evolving viral strains. The researchers found that immunizing animal models with surface proteins from related viruses, such as SARS-CoV-1, generated antibodies that met these criteria. The findings were published in Immunity.

“Our research aimed to identify a vaccination strategy that would target a key site of vulnerability on the virus surface that is unlikely to change over time. This site is unchanged in different coronavirus strains, meaning that the virus may be less likely to mutate to escape from an antibody immune response targeting this site,” says Deborah Burnett, first author of the paper.

The team tested different immunizations in mice that had been specialized to produce human antibody responses. Specifically, the researchers aimed to generate antibodies that target the ‘class 4 epitope’ region, which is conserved among coronaviruses (does not genetically vary between different strains) and may therefore be less likely to mutate in the future.

“Surprisingly, when we immunized with a protein from SARS-CoV-1, 80% of antibodies that were formed bound to the class 4 epitope. In contrast, when we used the SARS-CoV-2 protein, the mice generated antibodies that targeted regions of the coronavirus spike protein that are prone to mutations that allow the virus to easily escape,” she adds.

The researchers next set out to identify antibodies that not only bind to the SARS-CoV-2 class 4 epitope but can also block its entry into human cells. They analyzed thousands of individual antibody-producing B cells and pinpointed a rare subset of these ‘class 4’ antibodies that were able to neutralize the virus.  “To progress our proposed vaccine approach, we are now aiming to test next-generation vaccines in our preclinical models, to determine if they can generate these antibodies, which can protect against different strains of the virus,” concluded researcher Christopher Goodnow.