Researchers aim to uncover molecular signatures of vaccine efficacy in humans, which will guide design and rapid evaluation of new vaccines
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(HealthNewsDigest.com) – ATLANTA – The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) has awarded a five-year, $15.5 million grant to the Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, to study human immune responses to vaccination. Scientists in a new Center for Systems Vaccinology will employ the modern analytic tools of systems biology to understand the immune responses vaccines stimulate in humans and will use this knowledge to guide design of vaccines against HIV, malaria and other global pandemics.
Researchers at the center will address a major challenge thus far in the development of vaccines – that the effectiveness of vaccination can only be ascertained after vaccinated individuals have been exposed to infection. Bali Pulendran, PhD, Charles Howard Candler Professor in the Department of Pathology and Laboratory Medicine at Emory University, the Emory Vaccine Center and Yerkes Research Center, is principal investigator of the center. Rafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, will serve as co-PI. To study vaccine-induced immunity in humans, they will use a multidisciplinary approach Pulendran developed.
Pulendran’s approach, which he published in Nature Immunology in November 2008, involves immunology, genomics and bioinformatics to predict the immunity of a vaccine without exposing individuals to infection. This systems biological approach permits researchers to observe a global picture of all the nearly 30,000 genes, proteins and cells participating in immune responses to vaccination. Using this approach, the investigators were able to identify signatures of gene expression in the blood a few days after vaccination that could predict with up to 90 percent accuracy the strength of the immune response to the yellow fever vaccine, one of the most successful vaccines ever developed.
Researchers working in the new Center for Systems Vaccinology will determine whether Pulendran’s approach can be used to predict the effectiveness of other vaccines, including common vaccines against influenza, pneumococcal disease and shingles. With each of these vaccines, a substantial proportion of elderly individuals do not launch protective immunity. Researchers will work to identify gene signatures that would identify such individuals. The ability to successfully predict the immunity and efficacy of vaccines would facilitate the rapid evaluation of new and emerging vaccines, and the identification of individuals who are unlikely to be protected by a vaccine.
This effort will rely on the analysis of well-characterized young and elderly human cohorts, and use cutting-edge technologies such as genomics and proteomics to study the molecular and cellular dynamics of vaccine-induced immunity in humans with great precision. The center will comprise a highly integrated and interdisciplinary team of researchers and clinicians in areas as diverse as immunology, vaccinology, clinical medicine, computational modeling and mathematics.
The team members include Nick Haining, PhD (Dana Farber Cancer Institute, Boston); Eva Lee, PhD (Georgia Institute of Technology, Atlanta); Shankar Subramaniam, PhD (University of California, San Diego); Alex Sette, PhD (La Jolla Institute for Allergy and Immunology, La Jolla); Mark Mulligan, MD (Hope Clinic, Emory Vaccine Center); and Myron Levine, PhD, and Adriana Weinberg, PhD (University of Colorado, Denver).
The team’s initial work will focus on two major projects on innate immunity and adaptive immunity that ultimately will facilitate vaccine development in several ways: (1) by enabling a strategy to prospectively predict the immunogenicity of vaccines; (2) by offering new and fundamental insights into the genes, cells and networks that orchestrate vaccine induced immunity in the young and elderly; and (3) by facilitating the generation of an open access database of vaccine induced molecular signatures.
“We anticipate our collaborative research at the Center for Systems Vaccinology will address an important public health challenge in identifying novel biomarkers of vaccine efficacy. Such research will also synergize with studies in animal models to help understand the nature of the human immune response with an exquisite degree of depth and resolution,” says Pulendran.
Support for the first year of the initiative will come from the American Recovery and Reinvestment Act (ARRA).
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