ADITEC: Together working on next generation vaccines

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Scientists sit poised at a singular moment in the history of vaccine research. Genomics and systems biology have fuelled advances in our understanding of human immunology. Together with adjuvant development and structure-based design of immunogens, these next-generation technologies are transforming the field of vaccinology and shaping the future of medicine. However, the sophisticated science behind the development of modern vaccines and the resulting knotty ethical issues have become so complex that scientists and policy-makers need a new model for vaccine research. The European Commission–sponsored Advanced Immunization Technologies project — ADITEC — brings together some of the leading laboratories in the field to tackle the problems that no lab can tackle in isolation.

The tackling of some of the challenges of modern society—which include pandemic and seasonal influenza, human immunodeficiency virus (HIV) infection, tuberculosis, malaria, and the paucity of therapeutic vaccines—requires a change in the mind-set on how to conceive new effective vaccines and, consequently, the development of creative technologies that aid in the design of vaccines in the 21st century. Furthermore, modern vaccine development also requires new knowledge—both broadly applicable and pathogen-specific that illuminates the molecular mechanisms of human immunity, pathogen biology, and host-pathogen interactions. Diverse expertise and a spirit of collaboration are needed to meet these myriad challenges.

The ADITEC project is a 30 M€ High Impact Project (HIP) project funded by the European Commission that gathers 42 participants from 13 countries. Aditec comprises some of the most competitive European research groups from universities, research institutions, biotech companies and industry together with top US groups on systems biology and adjuvants.

Challenges and opportunities.

The majority of the vaccines available today have been developed empirically, using killed
or attenuated pathogenic microbes, without fully understanding the physiological mechanisms behind the resulting vaccine’s protective abilities. Modern vaccinology has many outstanding scientific questions about:
•    the characteristics and functions of powerful immunogens;
•    the mechanistic nature of protective immune responses;
•    how one can change the quality of an existing immune response;
•    mechanisms of the developing and aging human immune systems;
•    the nature and functions of host factors that influence susceptibility to and protection from disease.

Powerful new tools that can aid scientists in addressing these crucial questions are:

•    an enhanced ability to study human immunology;
•    the use of affordable genomic and systems biology techniques to identify new genomic, epigenomic, gene expression, proteomic, and metabolomics signatures that define the nature of protective immune responses and permit patient stratification in clinical trials; and
•    the ability to develop molecularly defined adjuvants that strengthen the immune response to vaccines by known mechanisms.

Approach

Advances in -omics technologies and systems biology along with an expanded focus on clinical immunology provide an opportunity to address vaccine-related scientific questions directly in human patients rather than relying on animal models. With the ability to characterize the immune response directly in human patients comes the capacity to investigate—at the molecular, cellular, tissue, and systems levels— how the human immune system responds to infection and immunization and then to use the information to design new or improved vaccines.
Studies in human subjects are expected to yield new Findings and raise new questions about fundamental mechanisms of immune responses that can then be studied in well-designed mouse models that mimic the relevant aspects of human physiology.

Systems biology approaches will be used to study existing and experimental vaccines in patient characterization studies and in clinical trials to investigate the effects of various vaccine components (adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous, and heterologous prime–boost schedules) and host factors. Animal models will be used to complement human studies and to select new immunization technologies to be advanced to the clinic.
The outcome of the new knowledge acquired by this multidisciplinary coordinated approach is expected to accelerate clinical de-velopment of new vaccines. The conventional “linear” approach of development tends to test single constructs first in animals and then in humans. The new paradigm is a “parallel” approach to vaccine development, in which participants in ADITEC will test many constructs at the same time.

Also part of ADITEC’s mandate is to contribute to the development of the next generation of scientists in the field of vaccinology.  An internationally recognized multilevel training program will be developed with the following aims: (i) contribute to the dissemination of knowledge in the field of translational immunology and vaccinology; (ii) improve and disseminate advanced research skills developed within the project; and (iii) promote mobility and exchanges between academia and industry.

Through the ADITEC project, the EC is providing the scientific community with a remarkable opportunity for uniting competencies toward a common goal: to design and develop next generation vaccines.