Analysis Shows Potential Targets for Immune Responses to Novel Coronavirus

Researchers at La Jolla Institute for Immunology have identified significant similarities in epitopes, or the specific structures that the immune system recognizes, between SARS-CoV-2, the virus associated with COVID-19, and other Betacoronaviruses, according to a new study.

For the study, which was published in Cell Host & Microbe, the researchers used available data from the Immune Epitope Database and Analysis Resource (IEDB) and the Virus Pathogen Resources (ViPR).

Though little information has been collected concerning which sequences of SARS-CoV-2 are recognized by human immune systems, and no epitope data are currently available for SARS-CoV-2, this information has been collected for coronaviruses in general, particularly for Betacoronaviruses such as SARS-CoV and MERS-CoV¬–both of which cause respiratory disease in humans.

SARS-CoV-2 is a novel coronavirus that originated in Wuhan, China in December 2019, and has since spread to every continent excluding Antarctica, with over 214,000 confirmed cases worldwide.

The IEDB houses epitope-related information under the issues of infectious disease, allergy, and autoimmunity, and additionally offers bioinformatic tools and algorithms which evaluate epitope data and predict potential epitopes for unknown sequences. ViPR has compiled information concerning human pathogenic viruses with regards to genome, gene, and protein sequences, and more specifically information about immune epitopes, protein structures, and host responses to virus infections.

The study utilized epitope information collected from the databases on Betacoronaviruses to identify likely targets of responses to SARS-CoV-2. The data showed an overall high level of sequence similarity between SARS-CoV and SARS-CoV-2, and researchers have inferred that the regions dominant in SARS-CoV are likely also dominant in SARS-CoV-2, even if the sequences themselves are different. 

B cell epitope predictions made by the IEDB based on protein conformation and residue exposure also confirmed 2 of the likely epitope regions; predictive algorithms for the T cell epitopes showed high sequence identity between SARS-CoV-2 and SARS-CoV.

“Right now, we have limited information about which pieces of the virus elicit a solid human response,” said lead study author Alessandro Sette, Dr Biological Sciences, professor in the Center for Infectious Disease and Vaccine Research at LJI. “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.”

The study concludes by stressing the importance of identifying the similarities between SARS-CoV-2 and SARS-CoV: “The observation that many B and T cell epitopes are highly conserved between SARS-CoV-2 and SARS-CoV is important. Vaccination strategies designed to target the immune response toward these conserved epitope regions could generate immunity that is not only cross-protective across Betacoronaviruses but also relatively resistant to ongoing virus evolution.”

References:

1. Grifoni A, Sidney J, Zhang Y, et al. A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell Host & Microbe. 2020;3(2). doi:https://doi.org/10.1016/j.chom.2020.03.002. Accessed March 17, 2020.