In the first study of its kind, researchers at the Yerkes National Primate Research Center and Emory Vaccine Center, Emory University, have developed a multidisciplinary approach involving immunology, genomics and bioinformatics to predict the immunity of a vaccine without exposing individuals to infection. This approach addresses a long-standing challenge in the development of vaccines--that of only being able to determine immunity or effectiveness long after vaccination and, often, only after being exposed to infection.
The study, which used the yellow fever vaccine (YF-17D) as a model, is available in the online edition of Nature Immunology and represents a long awaited step forward in vaccine immunology and predictive health.
YF-17D is one of the most successful vaccines ever developed and has been administered to nearly half a billion people over the last 70 years.
"A single shot of the vaccine induces immunity in many people for nearly 30 years," says Bali Pulendran, PhD, lead Yerkes researcher of the study and professor in the Department of Pathology and Laboratory Medicine at Emory University School of Medicine. "Despite the great success of the yellow fever vaccine, little has been known about the immunological mechanisms that make it effective," he continues.
Pulendran's team, including graduate student Troy Querec, PhD, in collaboration with Rafi Ahmed, PhD, director of the Emory Vaccine Center, Eva Lee, PhD, Georgia Institute of Technology, and Alan Aderem, PhD, Institute for Systems Biology in Seattle, sought to determine what makes such a vaccine effective so researchers can design new vaccines against global pandemics and emerging infections that repeat the success of this model vaccine.
The researchers used YF-17D to predict the body's ability shortly after immunization to stimulate a strong and enduring immunity. Researchers vaccinated 15 healthy individuals with YF-17D and studied the T cell and antibody responses in their blood. There was a striking variation in these responses between individuals. Analysis of gene expression patterns in white blood cells revealed in the majority of the individuals the vaccine induced a network of genes involved in the early innate immune response against viruses.
"Using a bioinformatics approach, we were able to identify distinct gene signatures that correlated with the T cell response and the antibody response induced by the vaccine," says Pulendran. "To determine whether these gene signatures could predict immune response, we vaccinated a second group of individuals and were able to predict with up to 90 percent accuracy which of the vaccinated individuals would develop a strong T or B cell immunity to yellow fever," continues Pulendran.
Pulendran and his colleagues are now working to determine whether this approach can be used to predict the effectiveness of other vaccines, including flu vaccines. The ability to successfully predict the immunity and effectiveness 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 type of research is essential to answer fundamental questions that can lead to better vaccinations and prevention of disease. Yerkes, as one of only eight National Institutes of Health-designated national primate research centers, is uniquely positioned to carry out such diverse research," says Stuart Zola, PhD, director, Yerkes Research Center.
Funding for this study was provided in part by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), as part of the U19 Cooperative Centers for Translational Research on Human Immunology and Biodefense.
Reference: Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nature Immunology, early online publication. Troy D. Querec, Rama S. Akondy, Eva K. Lee, Weiping Cao, Helder I. Nakaya, Dirk Teuwen, Ali Pirani, Kim Gernert, Jiusheng Deng, Bruz Marzolf, Kathleen Kennedy, Haiyan Wu, Soumaya Bennouna, Herold Oluoch, Joseph Miller, Ricardo Z. Vencio, Mark Mulligan, Alan Aderem, Rafi Ahmed and Bali Pulendran.
For nearly eight decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
The mission of the Emory Vaccine Center is to improve human health by conducting fundamental and clinical research that leads to the development of effective vaccines against infectious diseases of global importance. The Emory Vaccine Center represents one of the largest academic vaccine centers in the world, and is renowned for its expertise in cellular immunity and immune memory. This expertise leads to the creation of new technologies for the prevention of emerging infectious diseases.
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health center focused on missions of teaching, research, and health care. Its components include schools of medicine, nursing, and public health; Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.