Researchers at the Vanderbilt University Medical Center (VUMC) and the San Diego Supercomputer Center used advanced genetic sequencing and computational techniques to achieve the first step in how the human immune system responds to infections.
Their findings, published this week in Nature, can help develop "reasonable vaccine design" and improve the detection, treatment and prevention of autoimmune diseases, infectious diseases and cancer.
“Because of recent technological advances, we now have an unprecedented opportunity to use the power of the human immune system to fundamentally change human health,” said Wayne Koff, CEO of the Human Vaccine Program, which is responsible for research. Press Releases.
The focus of this study is on the production of white blood cells called antibodies, called B cells. These cells carry a Y-shaped receptor that, like a microscopic antenna, can detect a wide range of bacteria and other foreign invaders.
They do this by randomly selecting and joining a unique nucleotide sequence (DNA building block) called the receptor "clonal". In this way, a small number of genes can produce incredible receptor diversity, allowing the immune system to recognize almost any new pathogen.
It is daunting to understand exactly how this process works. "Before the current era, people thought that it would be impossible to do such a project because the immune system is so large in theory," said Dr. James Crowe, senior director of the Vanderbilt Vaccine Center.
"This new paper shows that a large part can be defined," Crow said. "Because the size of each person's B cell receptor library is unexpectedly small."
The researchers isolated white blood cells from three adults and cloned and sequenced up to 40 billion B cells to determine their clonotype. They also sequenced t cell receptor from cord blood from three infants. This sequencing depth has never been achieved before.
They found that the frequency of shared clonotypes was very high. "The overlap of antibody sequences between individuals is unexpectedly high," Crow explained. "It shows some of the same antibody sequences between adults and infants even at birth."
Understanding this commonality is key to identifying antibodies that can be used as vaccines and therapeutic antibodies targets, and these vaccines and treatments are more prevalent in the population.
The Human Vaccine Program is a non-profit, public-private partnership of academic research centers, industry, non-profit organizations, and government agencies dedicated to research and advancement of next-generation vaccines and immunotherapies. The study is part of the Human Immunization Program and aims to decode the genetic basis of the immune system.
As part of a unique alliance created by the Human Vaccine Project, the San Diego Supercomputing Center uses its considerable computing power to process terabytes of data. The core principle of the project is the merger of biomedical and advanced computing.
“The Human Vaccine Program allows us to research problems on a larger scale than is usually possible with a single laboratory, and to bring together groups that may not normally collaborate,” said Dr. Robert Sinkovits, who leads San Francisco’s scientific applications. Diego Supercomputer Center.
Collaborative work is currently underway to expand the study to sequence other areas of the immune system, from older people and B cells from around the world, and apply artificial intelligence-driven algorithms to further mine data sets for insight.
Researchers hope that continued trials of the immune system will eventually lead to the development of safer, highly targeted vaccines and immunotherapies that can work in the population.
"Resolving the human immune system is critical to addressing the global challenges of infectious and non-communicable diseases, from cancer to Alzheimer's disease to pandemic influenza," Cove said. "This study marks a key step in understanding how the human immune system works. The integration of genomics and immunosurveillance technology with machine learning and artificial intelligence has laid the foundation for the development of the next generation of healthy products."
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