Human Vaccines Project Studies Aim to Unveil Workings of Immune System

Scientists announced positive and encouraging outcomes from two clinical studies — running as part of the larger Human Vaccines Project — aiming to unravel the mechanisms that underlie our immune system’s ability to fight disease.

The results are expected to shed light on unknown aspects of the immune system that scientists at the Human Vaccines Project, a public-private partnership, hope to translate into new trials for diseases linked to the immune system, such as multiple sclerosis (MS).

Results from the trials — the Human Immunome Program and the Immunity to Hepatitis B Vaccine study — were recently presented at the World Vaccine and Immunotherapy Congress in San Diego, California.

In the ongoing Human Immunome Program (NCT03118687), researchers are trying to fill a major knowledge gap in the components and mechanisms of the immune system that allow it to recognize various threats, from viruses, parasites and bacteria to cancer cells.

They are using blood samples from healthy people to analyze, at an unprecedented depth, the whole repertoire of genes that make up the surface receptors of immune B- and T-cells, the core cells of the immune system’s defence mechanisms.

Results will likely advance how scientists diagnose and treat various diseases, and could prompt the development of new, improved vaccines.

“We are studying the immune systems of healthy individuals to identify common elements, which could be important for facilitating new and improved vaccines,” James E. Crowe Jr., MD, director of Vanderbilt University Medical Center’s Vaccine Center, the leading scientific institution of the Human Immunome Program, said in a press release.

Researchers will cross the sequencing information with participants’ microbiome composition — the natural community of microbes that reside in an organism and are key for a healthy immune system — and other health and sociodemographic characteristics.

“We also plan to expand these studies to complete the catalog across different demographics and geographies and compare healthy subjects with individuals with immune-mediated diseases such as multiple sclerosis, cancer and Alzheimer’s, which could also reveal novel diagnostic markers,” Crowe said.

The second study, the Immunity to Hepatitis B Vaccine trial (NCT03083158) — currently recruiting participants — aims to understand why some people achieve protection against Hepatitis B after a single vaccine shot, while others require up to three immunizations to acquire full immunity.

Understanding why the immune system responds differently in individuals can help researchers improve existing vaccines and potentially lead to one-shot vaccines that provide long-term immunity for all populations.

Researchers in this study are analyzing genes belonging to the innate-immune system — a general immune system response, not one tailored to specific threats — and observing that activation of these genes in certain immune cells can predict who will be a responder after a single shot of the Hepatitis B vaccine.

Preliminary results of the Immunity to Hepatitis B Vaccine study were delivered in two separate sessions at the congress. One was given by Manish Sadarangani, director of the Vaccine Evaluation Center of the University of British Columbia and BC Children’s Hospital Research Institute, and the by and Richard Scheuermann, director of the J. Craig Venter Institute in La Jolla, California.

“These preliminary data points toward strategies to understand why some people respond better to vaccines than others,” Sadarangani said.

“Using single cell analyses, we now have the opportunity to probe vaccine-induced responses more effectively, to not only learn what happens immediately after vaccination, but to monitor responses over time and utilize machine learning to eventually predict the human immune response to vaccines,” added Scheuermann.

Wayne C. Koff, president and chief executive officer of the Human Vaccines Project, emphasized that researchers are optimistic with the results obtained so far, as they “provide important insights into the scale and complexity of the human immune system and how vaccines confer protective immunity.”

“With our network of academic and corporate partners, we aim to build on these findings and decode the human immune system, giving the world the tools required to advance the development of future vaccines and therapies to defeat major global diseases,” Koff concluded.