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Vanderbilt, human vaccines project launch studies to decode human immune system

June 21, 2016

Researchers at Vanderbilt University Medical Center this month began recruiting volunteers to participate in a clinical trial aimed at decoding the human "immunome," the genetic underpinnings of the immune system.

The study is the first phase of an international effort led by the Human Vaccines Project, a public-private partnership of academic research centers, industry, non-profits and government agencies designed to accelerate the development of next-generation vaccines and immunotherapies.

"I am tremendously excited to launch the Project's Human Immunome Program, and look forward to generating important new data that should facilitate vaccine design for both infectious diseases and cancers," said James Crowe Jr., M.D., director of the Vanderbilt Vaccine Center, in a news release.

"The Project remains committed to rapid, open source communication of these data, to enable the community of global scientists to advance new and fundamental insights on how the human immune system can be mobilized more effectively to fight disease," Crowe said.

Progress against infectious diseases and cancer has been hampered by inadequate understanding of the principal components of the immune system, particularly the massive collection of receptors on B and T cells. These cells and their receptors enable the immune system to recognize, adapt to and attack an extraordinarily large number of disease threats.

Thanks to recent advances in genomics, systems biology and bioinformatics, researchers have been able to sequence and characterize many of these receptors. Such information is critical to engineering highly targeted vaccines and therapies to confront major infectious diseases and emerging pandemics, as well as autoimmune disorders and cancer.

"For the first time we have the technological tools to undertake such an ambitious project to decode the human immune system," said Wayne C. Koff, Ph.D., President and CEO of the Human Vaccines Project.

"As the Human Genome Project has ushered in a new era in precision medicine, the Human Vaccines Project has the potential to enable a new era of vaccine and immunotherapeutic development against some of the world's most pressing diseases," Koff said.

As a first step of the pilot study at VUMC, two healthy individuals will undergo leukapheresis, a blood donation process in which large numbers of circulating white blood cells are removed by filtration, while red blood cells are returned to the donor.

After the genetic sequences of all of the receptors on the white blood cells from each individual have been determined, the study will be expanded to include about 100 subjects, representing different ages, genders, ethnicities and geographies.

This will then form the baseline set of data to expand the study to more than 1,000 subjects, a subset of whom will be vaccinated with licensed and experimental vaccines. Insights about the fundamental principles of human immunology gained from this study will help guide next generation vaccine development.

The number of sequences acquired from them could be in the billions, and will constitute the first detailed account of the immunome, said Crowe, who is the Ann Scott Carell Professor and professor of Pediatrics and Pathology, Microbiology and Immunology.

Crowe and his colleagues will collaborate with one of the Project's scientific hubs in La Jolla, California, which is made up of the J. Craig Venter Institute (JCVI), La Jolla Institute for Allergy and Immunology, University of California, San Diego and The Scripps Research Institute.

JCVI and the San Diego Supercomputer Center at UC San Diego will serve as the Project's global Bioinformatics Core.

The Human Vaccines Project will fund the project. Because it can cost more than $100,000 to acquire the genetic repertoire from each individual's white blood cells, due to the large amount of sequencing required, eventually more than $100 million will be needed to fully decipher the human immunome, officials said.

But if the complete sequence of the human immunome could be achieved in a decade, it would be a "major achievement," said Nobel Laureate Peter Doherty, Ph.D., a member of the Human Vaccines Project Scientific Steering Committee and Professor at the University of Melbourne.

It would "greatly advance our understanding of the human immune system, enabling rational and targeted design of vaccines and immunotherapies for major global diseases," Doherty said.
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Vanderbilt University Medical Center

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