May 9, 2024

UCLA Breakthrough Points Way to Longer-Lasting COVID Vaccine

One way to achieve this is by including a fragment of a different viral protein to vaccines– one that is less susceptible to anomalies than the spike protein and that will activate the body immune systems T cells. T cells are geared up with molecular receptors on their surface areas that acknowledge foreign protein fragments called antigens. When a T cell encounters an antigen its receptor acknowledges, it self-replicates and produces extra immune cells, some of which target and eliminate infected cells right away and others which remain in the body for decades to eliminate that very same infection needs to it ever return.
The researchers concentrated on the viral polymerase protein, which is discovered not just in SARS-CoV-2 but in other coronaviruses, consisting of those that trigger SARS, MERS and the cold. Viral polymerases act as engines that coronaviruses use to make copies of themselves, allowing infection to spread. Unlike the spike protein, viral polymerases are not likely to change or alter, even as infections develop.
To figure out whether the human body immune system has T cell receptors efficient in acknowledging viral polymerase, the scientists exposed blood samples from healthy human donors (collected prior to the COVID-19 pandemic) to the viral polymerase antigen. They found that certain T cell receptors did, in truth, acknowledge the polymerase. They then utilized a method they established called CLInt-Seq to genetically sequence these receptors. Next, the researchers engineered T cells to carry these polymerase-targeting receptors, which allowed them to study the receptors capability to eliminate and acknowledge SARS-CoV-2 and other coronaviruses.
More than 5 million individuals have died from COVID-19 worldwide. Current vaccines supply considerable security against severe illness, however as brand-new, potentially more infectious variations emerge, researchers recognize that vaccines might require to be updated– and the brand-new UCLA findings point toward a method that might help increase security and long-lasting immunity. The researchers are now performing additional studies to assess viral polymerase as a prospective new vaccine part.
The research study was released online on December 9, 2021, in the journal Cell Reports.
Referral: “HLA-A * 02:01 restricted T cell receptors versus the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses” by Pavlo A. Nesterenko, Jami McLaughlin, Brandon L. Tsai, Giselle Burton Sojo, Donghui Cheng, Daniel Zhao, Zhiyuan Mao, Nathanael J. Bangayan, Matthew B. Obusan, Yapeng Su, Rachel H. Ng, William Chour, Jingyi Xie, Yan-Ruide Li, Derek Lee, Miyako Noguchi, Camille Carmona, John W. Phillips, Jocelyn T. Kim, Lili Yang, James R. Heath, Paul C. Boutros and Owen N. Witte, 9 December 2021, Cell Reports.DOI: 10.1016/ j.celrep.2021.110167.
Pavlo Nesterenko, a UCLA graduate student, is the research studys very first author; the matching author is Dr. Owen Witte, who holds the governmental chair in developmental immunology in the UCLA Department of Microbiology, Immunology and Molecular Genetics and is establishing director emeritus of the Broad Stem Cell Research. A full list of co-authors is available in the journal.
The research study was supported by the Parker Institute for Cancer Immunotherapy, a Ruth L. Kirschstein Institutional National Research Service Award from the National Institutes of Health and the UCLA W.M. Keck Foundation COVID-19 Research Award Program.

Microscopic lense image showing a human cell (pink) heavily contaminated with SARS-CoV-2 virus particles (purple and green). Credit: NIAID/NIH
Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have determined unusual, naturally occurring T cells that are capable of targeting a protein discovered in SARS-CoV-2 and a series of other coronaviruses.
The findings recommend that a component of this protein, called viral polymerase, could possibly be contributed to COVID-19 vaccines to produce a longer-lasting immune action and increase security versus new versions of the virus.
The majority of COVID-19 vaccines use part of the spike protein found on the surface of the infection to trigger the body immune system to produce antibodies. More recent versions– such as delta and omicron– carry anomalies to the spike protein, which can make them less recognizable to the immune cells and antibodies promoted by vaccination. Scientists state that a new generation of vaccines will likely be required to develop a more wide-ranging and robust immune action capable of repeling existing variants and those that may arise in the future.

One way to achieve this is by adding a piece of a various viral protein to vaccines– one that is less prone to mutations than the spike protein and that will activate the immune systems T cells. When a T cell encounters an antigen its receptor acknowledges, it self-replicates and produces extra immune cells, some of which target and kill contaminated cells instantly and others which remain in the body for years to fight that exact same infection should it ever return.
To determine whether or not the human immune system has T cell receptors capable of recognizing viral polymerase, the researchers exposed blood samples from healthy human donors (collected prior to the COVID-19 pandemic) to the viral polymerase antigen. Next, the researchers engineered T cells to carry these polymerase-targeting receptors, which enabled them to study the receptors ability to recognize and eliminate SARS-CoV-2 and other coronaviruses.