Tag: coronavirus outbreak

LJI scientists identify potential targets for immune responses to novel coronavirus

LA JOLLA, CA—Within two months, SARS-CoV-2, a previously unknown coronavirus, has raced around globe, infecting over a 100,000 people with numbers continuing to rise quickly. Effective countermeasures require helpful tools to monitor viral spread and understand how the immune system responds to the virus.

Publishing in the March 16, 2020, online issue of Host, Cell and Microbe, a team of researchers at La Jolla Institute for Immunology, in collaboration with researchers at the J. Craig Venter Institute, provides the first analysis of potential targets for effective immune responses against the novel coronavirus. The researchers used existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system.

When the immune system encounters a bacterium or a virus, it 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. Having 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.  

“Right now, we have limited information about which pieces of the virus elicit a solid human response,” says the study’s lead author Alessandro Sette, Dr. Biol.Sci, a 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.”

While scientists currently 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.

Four other 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 few years, 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.

“SARS-CoV-2 is most closely related to SARS-CoV, which also happens to be the best characterized coronavirus in terms of epitopes,” explains first author Alba Grifoni, Ph.D, a postdoctoral researcher in the Sette lab

For their study, the authors 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 team compiled known epitopes from SARS-CoV and mapped the corresponding regions to SARS-CoV-2.

“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-CoV are also dominant in SARS-CoV-2 is,” says Grifoni. 

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. 

In a similar analysis, T cell epitopes were also mostly associated with the spike glycoprotein and nucleoprotein.

In a completely different approach, 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 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 substantiate the SARS-CoV-2 T cell epitopes identified based on their homology to SARS-CoV, Grifoni compared them with epitopes pinpointed by the Tepitool resource in the IEDB. Using this approach, she was able verify 12 out of 17 SARS-CoV-2 T cell epitopes identified based on sequence similarities to SARS-CoV. 

“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,” says Sette. “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 work was funded in part by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health through contracts 75N9301900065, 75N93019C00001 and 75N93019C00076.

Full citation: Alba Grifoni, John Sidney, Yun Zhang, Richard H Scheuermann, Bjoern Peters and Alessandro Sette. A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell, Host and Microbe, 2020.

A pre-proof is available here.

About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

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Two New Rapid Tests Could Play Key Role in Efforts to Contain Growing Epidemic

WASHINGTON – Breaking research in AACC’s Clinical Chemistry journal shows that two new tests accurately diagnose coronavirus infection in about 1 hour. These tests could play a critical role in halting this deadly outbreak by enabling healthcare workers to isolate and treat patients much faster than is currently possible. 

Since the coronavirus emerged in Wuhan, China last month, this pneumonia-like illness has spread at an alarming rate. Just yesterday, the World Health Organization officially declared the outbreak a public health emergency, and as of today, the virus has infected nearly 10,000 people in China, with the death toll soaring to more than 200. More cases continue to appear around the globe, with six coronavirus cases already confirmed in the U.S. In order to contain this pandemic, healthcare workers need to quickly and accurately identify new coronavirus cases so that patients get crucial medical care and transmission can be halted. However, the Chinese labs that can test for coronavirus are currently overwhelmed. There are reports of hospitals in Wuhan having to deny testing for severely ill patients, who are then also denied full-time admission because beds need to be saved for those with confirmed diagnoses. Partly as a result of these testing difficulties, researchers estimate that only 5.1% of coronavirus cases in Wuhan have actually been caught. 

A team of researchers led by Leo L.M. Poon, DPhil, of the University of Hong Kong has developed two rapid tests for the coronavirus that could break this diagnostic bottleneck. Using a technology known as real-time reverse transcription polymerase chain reaction (RT-PCR), the tests detect two gene regions that are only found in the Wuhan coronavirus (officially known as 2019-novel-coronavirus) and in other closely related coronaviruses such as SARS. The two gene regions detected by the tests are known as ORF1b and N. Significantly, both tests also take only about 1 hour and 15 minutes to run. This fast turnaround time could enable Chinese labs to greatly increase patient access to coronavirus testing. 

To evaluate the performance of these tests, Poon’s team first confirmed that the tests accurately identify genetic material extracted from cells infected with the SARS coronavirus. The researchers also showed that the tests return negative results for samples containing genetic material from other respiratory viruses, demonstrating that the tests accurately differentiate coronavirus infection from other causes of pneumonia. Lastly, Poon’s team used the tests to analyze sputum and throat swab samples from two patients infected with the 2019-novel-coronavirus. The tests correctly gave positive results for both patients. 

“Signs of [coronavirus] infection are highly non-specific and these include respiratory symptoms, fever, cough, [shortness of breath], and viral pneumonia,” said Poon. “Thus, diagnostic tests specific for this infection are urgently needed for confirming suspected cases, screening patients, and conducting virus surveillance. The established assays [in this study] can achieve a rapid detection of 2019-novel-coronavirus in human samples, thereby allowing early identification of patients.”

About AACC

Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.aacc.org

Clinical Chemistry (clinchem.org) is the leading international journal of laboratory medicine, featuring nearly 400 peer-reviewed studies every year that help patients get accurate diagnoses and essential care. This vital research is advancing areas of healthcare ranging from genetic testing and drug monitoring to pediatrics and appropriate test utilization.