A bold, new, global non-profit partnership seeks to establish a German Vaccine Research and Development Center (GVRDC) The Human Vaccine Project

German Vaccine Research and Development Center (GVRDC): The Human Vaccines Project is seeking €25 million support from the government of Germany to establish the German Vaccine Research and Development Center linking German researchers into a world-class research network of academic, government and industrial research and development partners, and serving as the Project’s principal European hub.  We envision the GVRDC will focus on research and development of vaccines, immunotherapies and diagnostics for diseases of importance to Germany, Europe and the developing world, and on scientific questions which impact development of new and improved vaccines for the world.   In affiliation with the Project, the GVRDC will employ the latest technologies in genomics and bioinformatics to understand mechanisms of protective immunity and rationally develop next generation vaccines, diagnostics and immunotherapies. This will be accomplished by:

• Fundamental Research in Human Immunology. By advancing our fundamental knowledge of human immunity, scientists can change the paradigm of how vaccines and immunotherapies are developed. Work under this area is driven by extensive clinical research, systems biology and genomics/proteomics- based studies and coupled with advances in bioinformatics and machine learning to fill in fundamental gaps in our knowledge of human immunity. GVRDC-led studies will be integrated and synergize with global studies and include:

1. Determining the Principles of Immunity: The primary goal of the Human Vaccines Project is to determine the mechanisms of effective human immunity by intensive systems-biology studies to determine differences between responders vs. non-responders to vaccines and immunotherapies. By determining the underlying mechanisms responsible for potent long-term immunity that protects across populations and demographics, we have the unprecedented opportunity to change the future of disease prevention and treatment for a wide range of diseases. Systems immunology studies are now able to provide unique insights into mechanisms of immunity, and the Human Vaccines Project has employed these technologies to begin decoding the human immune system.   For example, in an initial study using the Hepatitis B virus (HBV) vaccine, an ideal model system as there is a clear and easily measurable correlate of protection, the Project used single cell RNA sequencing (scRNA-seq) to show that expression of specific markers in myeloid dendritic cells can predict response to a single HBV vaccine dose.  Moreover, data integration of multi-OMIC, molecular and cellular preimmunization data generated biostatistical models that predicted final antibody titers after 3 HBV vaccine doses. These findings suggest that individuals have a baseline “immune setpoint”, which can accurately predict vaccine responses to hepatitis B immunization. By applying a systems immunology approach to the study of other vaccines, we open the door to uncovering previously unknown mechanisms of immunity and the potential to modify and improve vaccines and immunotherapies, bringing the goal of effective single-dose vaccines or immunotherapies in all populations much closer to reality.  The Human Vaccines Project plans to build on these observations by studying vaccines against other pathogens, and immunotherapies for cancer and other non-communicable diseases.
   1. GVRDC Objective: Under this program, the GVRC will lead European efforts to conduct trials to determine the mechanisms of protective immunity through an iterative set of clinical studies consistent with Human Vaccines Project protocols and bioinformatic platforms, with comprehensive monitoring and analyses of human immune responses. Selection and prioritization of studies will be reviewed annually by the Project’s independent Scientific Steering Committee, to ensure integration with the Project’s global scientific objectives.
   2. Estimated Budget: €15 Million.

1. Sequencing the Human Immune System (the Human Immunome): By determining the genetic foundations of the human immune system, we have the potential to design highly targeted and safer vaccines and immunotherapies for a wide-range of diseases. Under the Human Immunome Program, the Project has already started a large-scale effort in the US to determine for the first time the universe and common elements of the adaptive immune system (defined as the full-range of B and T cell receptors across age and population). The GVRDC would lead a European effort decipher the immunomes of Europeans and persons living in the developing world to expand a worldwide open source data base of immune receptors that will be open to the global research community.
   1. GVRDC Objective: Decipher a minimum of 100 human immunomes, the universe of B cell receptors and T cell receptors per volunteer, utilizing standard sequencing protocols and bioinformatics platforms consistent with those developed by the Human Vaccines Project. It is anticipated that the 100 subjects would be varied by age, gender, and host genetics, with a minimum of 50% of subjects originating from the developing world.
   2. Estimated Budget: €5 million

• Portfolio Management, Bioinformatics and Data Management: The scale and complexity of biomedical research data generated by the Human Vaccines Project is unprecedented and dwarfs the scale of data generated by the Human Genome Project due to the complexity of the human immune system. As a result, the Human Vaccines Project has established portfolio management, bioinformatics, and data management units to enable integration of data with standardized protocols across a global network.   Affiliation and integration of the GVRDC in the Human Vaccines Project network requires additional resources specifically dedicated to these central hubs of the Project and training modules for GVRDC staff.
  1. Estimated Budget: €5 million

Conclusion:  The global scientific community is at a critical turning point in its potential to combat disease driven by a host of new technologies that are allowing us to understand and harness the human immune system in ways not thought possible even a decade ago. The creation of the GVRDC in affiliation with the Human Vaccines Project would augment the premier global network of scientists working to realize the potential of vaccination, and greatly accelerate efforts in this area through world-class research, cutting edge technology and visionary financing.

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