Study Team Identifies Targets for COVID-19 Vaccine

New analyses of the novel coronavirus structure and the immunologic response provoked by the similar, previously circulating SARS virus reveal potential targets for a vaccine-heightened B and T cell defense, according to investigators from the La Jolla Institute for Immunology (LJI), La Jolla, California.

"Knowing the immunogenicity of certain viral regions, or in other words, which parts of the virus the immune system reacts to and how strongly, is of immediate relevance for the design of promising vaccine candidates and their evaluation," explained principal Investigator Alessandro Sette, Dr Biol Sci.

In their study published in Cell, Sette and colleagues describe taking multiple analytical approaches to characterize the SARS-CoV-2 virus responsible for Coronavirus Disease 2019 (COVID-19). These included identifying the immunodominant regions that are homologous to those in SARS-CoV, the coronavirus that caused Severe Acute Respiratory Syndrome (SARS) in 2003. In addition, they applied an algorithm developed to predict antigen epitopes, molecular structures recognized by the immune system, to predict linear B cell targets on SARS-CoV-2.

Sette and colleagues credit investigators at the University of Texas Austin for determining the 3-dimensional structure of the spike glycoprotein on the virus surface which forms the "crown"— that inspired the corona name—and enabled them to refine their epitope predictions.

Their analysis revealed that T cell epitopes are principally in the spike glycoprotein and nucleoprotein. Five of the B cell epitope regions are in the spike glycoprotein, 2 in the membrane protein, and 3 in the nucleoprotein of the virus shell.

"We were able to map back 10 B cell epitopes to the new coronavirus, and because of the overall high sequence similarity between SARS-CoV and SARS-CoV-2, there is a high likelihood that the same regions that are immunodominant in SARS-CpV are also dominant in SARS-CoV-2," said lead author Alba Grifoni, PhD.

The investigators also utilized an epitope prediction algorithm hosted by the LJI-based Immune Epitope Database and Analysis Resource (IEDB). That resource, which contains over 600,000 known epitopes from approximately 3600 different species, was used in conjunction with the Virus Pathogen Resource (ViPR), a complementary repository of information about human pathogenic viruses. Their application of the algorithm confirmed 2 of the epitope regions on the crown that were predicted in the initial analysis.

"The fact that we found that many B and T cell epitopes are highly conserved between SARS-CoV and SARS-CoV-2 provides a great starting point for vaccine development," Sette said. "Vaccine strategies that specifically target these regions could generate immunity that's not only cross-protective but also relatively resistant to ongoing virus evolution."

In another recently published evaluation of potential epitopes for SARS-CoV-2 based largely on study of the previously circulating SARS-CoV, investigators in Hong Kong performed a population coverage analysis of their candidate T cell epitopes.

"T cell responses have been shown to provide long-term protection, even up to 11 years post-infection, and thus have also attracted interest for a prospective vaccine against SARS-CoV," wrote lead author Syed Ahmed, PhD graduate student, Hong Kong University of Science and Technology, and colleagues.

Ahmed and colleagues accessed the IEDB to identify a set of multiple T cell epitopes associated with 20 distinct MHC alleles, which they estimate provide an accumulated population coverage of 96.29%.

"Our aim was to determine sets of epitopes associated with MHC alleles with maximum population coverage, potentially aiding the development of vaccines against SARS-CoV-2," they wrote.