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Researchers at Boston Children’s Hospital’s Precision Vaccines Program develop new tool to identify cellular and molecular signatures of vaccines

Over 200 years have passed since the first vaccine was developed, and researchers now have the data and computational power required to understand why different individuals respond to vaccines differently. In collaboration with colleagues in the Human Immunology Project Consortium (HIPC), scientists at Boston Children's Hospital created a new tool to help researchers understand these differences and, hopefully, design safer, more effective vaccines. The Immune Signatures Data Resource, spearheaded by Joann Diray-Arce, PhD, and co-authored by Ofer Levy, MD, PhD, Director of Boston Children’s Precision Vaccines Program, was published Oct. 20 in Scientific Data.

The HIPC was established by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and is funded by NIAID.

“We currently have vaccines against a range of infectious diseases, but still lack a molecular understanding of how vaccines protect. This project was an opportunity for the scientific community to work together in synergy to standardize ways of defining and comparing molecular signatures of vaccine-induced protection,” says Diray-Arce, the paper's first author.

The Immune Signatures Data Resource is the first large-scale, standardized dataset for examining vaccine-induced cellular and molecular signatures in humans. It contains demographic, genetic, and immunologic data from 53 studies covering 24 different vaccines, including those protecting against yellow fever, influenza, smallpox, pneumonia, Ebola, Hepatitis B, human immunodeficiency virus (HIV), tuberculosis, pneumonia, and chickenpox.

A team of HIPC collaborators partnered under the leadership of Steven Kleinstein, PhD, the Anthony N. Brady Professor of Pathology at Yale School of Medicine, to build this data analysis tool with the potential to advance vaccine development. The HIPC team collected data from peer-reviewed publications on how people respond to vaccines and submitted them to ImmPort, a NIAID-funded portal, to share data with the public. For older published studies without publicly available datasets, Diray-Arce tracked down the authors’ contact information and reached out to the scientists personally to obtain and upload their data. The HIPC team then used computational tools in a web-based analytics platform called ImmuneSpace to standardize the dataset, allowing researchers to compare gene expression profiles and antibody responses across 1,405 individuals from the different studies.

This data resource is now publicly available for a range of follow-up studies. The tool has already enabled two publications in Nature Immunology, in which Diray-Arce, Levy, and coauthors suggest that baseline activity of a protein of the innate immune system known as nuclear factor-kappa B (NF-κB), as well as the timing of immune system reactions, play essential roles in the protectiveness of vaccines.

The Precision Vaccines Program’s ultimate goal is to leverage the comprehensive dataset to develop vaccines that offer broad, long-lasting protection against infectious diseases. Specifically, the researchers are excited to understand better the mechanisms by which certain live weakened pathogens protect, such as the yellow fever vaccine, which provides long-term defense against disease, and the Bacille Calmette-Guérin (BCG) tuberculosis vaccine, which unexpectedly shields newborns against a range of unrelated bacterial and viral infections. “We are turning big data into knowledge. As we define cellular and molecular signatures associated with protective immune responses, we can better develop vaccines that improve immunity in vulnerable populations,” says Levy.

HIPC investigators on this project are from Fred Hutchinson Cancer Research Center, NIH, Cambridge University, Emory University School of Medicine, Yale University, Stanford University, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Icahn School of Medicine at Mount Sinai, University of California San Francisco, The Jackson Laboratory for Genomic Medicine, NG Health Solutions, Columbia University Medical Center, and University of Lausanne.