T cells found in coronavirus patients 'bode well' for long-term immunity

James Marshall
May 22, 2020

A dedicated SARS-CoV-2 multidisciplinary genomic response team from the Victorian Infectious Diseases Reference Laboratory (VIDRL) and the Microbiological Diagnostic Unit Public Health Laboratory (MDU-PHL) at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), and the Victorian Department of Health and Human Services (DHHS) was formed to link epidemiological and genomic data of Victoria's coronavirus (COVID-19) cases and assess the impact of social restrictions. An global team of scientists isolated antibodies from a SARS survivor's "memory B cells" Memory B cells form after an infectious illness, and usually remember the pathogen (or a similar one) that it had fought it back earlier.

Y. Konno et al., "SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant", bioRxiv, doi:10.1101/2020.05.11.088179, 2020.

"Right now there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19", he added.

From the SARS survivor's memory B cells, the scientists identified a number of monoclonal antibodies. If a new infection happens, these cells launch an antibody counterattack again. In a preprint posted on bioRxiv on May 12, researchers have shown in cell culture that a viral protein called open reading frame 3b (ORF3b) actively blocks the induction of type I interferon, a crucial aspect of that response. The ORF3b proteins that were best at inhibiting the interferon response were from SARS-CoV-2 and closely related coronaviruses, as well as two proteins from bat viruses related to SARS-CoV that also had shorter ORF3b proteins.

In addition, the researchers also obtained the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the Spike-ectodomain trimer.

Miles to go: It is important to note that the action of S309 has only been demonstrated in the lab.

This means donated plasma from survivors might save lives, Dr. Mehul Suthar with Emory University School of Medicine said. The antibody is now on a fast-track development and testing path at the company Vir Biotechnology in the next step toward possible clinical trials, the University said. Moreover, they showed that SARS-CoV-2 neutralizing antibodies could be selected with high efficiency based on similarities of their predicted structures to those of SARS-CoV neutralizing antibodies, hence greatly expediting the screening process. Citing this report, the Scripps Institute in the U.S. said in April that its researchers have now done structural mapping to determine how the antibody binds to SARS-CoV-2. It revealed the antibody's epitope overlaps with the ACE2 binding-site, which provides the structural basis of neutralization. However, the antibody binds much less tightly to SARS-CoV-2 than it does to the SARS virus. They noticed the SARS-CoV-2 ORF3b is considerably shorter than its SARS-CoV ortholog, encoding a protein just 22 amino acids long, compared to the 154 amino acids of SARS-CoV ORF3b, thanks to the presence of premature stop codons. Other antibodies binding it more tightly would plausibly succeed in neutralising the virus, the Scripps Institute said.

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