Latest Coronavirus Research: Epitopes Of SARS-Cov-2 Coronavirus Identified As Potential Targets For Immune Response
: Medical researchers from La Jolla Institute for Immunology, together with virology experts from the J. Craig Venter Institute have isolated potential targets for effective immune responses against the SARS-Cov-2 coronavirus which causes the deadly Covid-19 disease.
The team utilized existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system. (https://marlin-prod.literatumonline.com/pb-assets/journals/research/cell-host-microbe/PDFs/CHOM_2264_S50.pdf
Research utilized existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system. Credit: Grifoni et al./Cell Host & Microbe
Understanding how the human immune system responds to the virus is critical in helping to develop effective countermeasures required to stop the viral spread and to treat it.
The human immune system upon encountering a virus, zeroes in on tiny molecular features, so called epitopes, which allow cells of the immune system to distinguish between closely related foreign invaders and focus their attack.
Possessing a complete map of viral epitopes and their immunogenicity is critical to researchers attempting to design new or improved vaccines to protect against COVID-19, the disease caused by SARS-CoV-2.
Dr Alessandro Sette, A Professor in the Center for Infectious Disease and Vaccine Research at La Jolla Institute and the main lead author of the research told Thailand Medical News, "Currently, we have limited information about which pieces of the virus elicit a solid human response. Recognizing 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."
Though medical experts at the moment know very little about how the human immune system responds to SARS-CoV-2, the immune response to other coronaviruses has been studied and a significant amount of epitope data is available.
There are four other non-zoonotic coronaviruses are currently circulating in the human population. They cause generally mild symptoms and together they are responsible for an estimated one quarter of all seasonal colds. But every once in a while, a new coronavirus emerges that causes severe disease as was the case with SARS-CoV in 2003 and MERS-CoV in 2008, and now SARS-CoV-2.
Dr Alba Grifoni, Ph.D, a postdoctoral researcher in the Sette lab and first author of the study said, "SARS-CoV-2 is most closely related to SARS-CoV, which also happens to be the best characterized coronavirus in terms of epitopes."
In the research, the scientists used available data from the LJI-based Immune Epitope Database (IEDB), which contains over 600,000 known epitopes from some 3,600 different species, and the Virus Pathogen Resource (ViPR), a complementary repository of information about pathogenic viruses.
The research team also compiled known epitopes from SARS-CoV and mapped the corresponding regions to SARS-CoV-2.
Dr Grifoni added, "The team was 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-CoV are also dominant in SARS-CoV-2.”
The research team observed that five of these regions were found in the spike glycoprotein, which forms the "crown" on the surface of the virus that gave coronaviruses their name; two in the membrane protein, which is embedded in the membrane that envelopes the protective protein shell around the viral genome and three in the nucleoprotein, which forms the shell.
Similar detailed analysis also showed that T cell epitopes were also mostly associated with the spike glycoprotein and nucleoprotein.
Utilizing a unique approach, Dr Grifoni used the epitope prediction algorithm hosted by the IEDB to predict linear B cell epitopes. A recent study by scientists at the University of Texas Austin had already determined the three-dimensional structure of the spike proteins, which allowed the LJI team to take the protein's spatial architecture into account when predicting epitopes. This approach confirmed two of the likely epitope regions they had predicted earlier.
To further confirm and substantiate the SARS-CoV-2 T cell epitopes identified based on their homology to SARS-CoV, Dr Grifoni compared them with epitopes pinpointed by the Tepitool resource in the IEDB.
Utilizing this method, she was able verify 12 out of 17 SARS-CoV-2 T cell epitopes identified based on sequence similarities to SARS-CoV.
Dr Sette commented, "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. Vaccine strategies that specifically target these regions could generate immunity that's not only cross-protective but also relatively resistant to ongoing virus evolution."
The study has been published in the March 16, 2020, online issue of Cell, Host and Microbe.
The research findings will be extremely useful for the various teams worldwide currently working on developing a vaccine against the Covid-19 disease that is caused by the SARS-CoV-2 coronavirus.
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Reference: Alba Grifoni et al. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2 Cell, Host, and Microbe https://marlin-prod.literatumonline.com/pb-assets/journals/research/cell-host-microbe/PDFs/CHOM_2264_S50.pdf DOI: 10.1016/j.chom.2020.03.002
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