What is the project work plan?

The overall objective of the PERISCOPE consortium is to accelerate the development and registration of novel pertussis vaccines. Pivotal to this is the identification of novel biomarkers of protection and the development of models that can be used to expedite preclinical and clinical testing, and selection of the most effective candidates for licensing. To achieve these objectives, the project is divided into seven distinct work packages:

• WP 1: Studies on immune response to infection and vaccination in relevant pre-clinical models
  In WP1 we will establish a pre-clinical model for B. pertussis colonisation and disease in Europe, which is currently the only model that accurately reflects clinical pertussis in humans. In PERISCOPE, we will primarily use this model as an exploratory model to identify putative biomarkers of protection against colonisation and disease and understand mucosal responses to infection. Furthermore, it will serve to cross-validate biomarker findings from the human vaccination studies (WP3) and their correlation with vaccine-mediated protection.
• WP 2: Immunological studies of B. pertussis infection in human volunteers naturally exposed to pertussis or via controlled challenge studies

  In WP2 we will develop a human challenge model in healthy adult volunteers (18-45y) for B. pertussis colonisation. Comparison of protection levels, due to previous vaccination or exposure, in challenged individuals will allow us to identify, and substantiate, biomarkers that are associated with protection against colonisation. Notably, colonisation is the primary clinical endpoint of this model. We will also study immunity to infection in human patients across different age groups. This will allow us to compare immunological parameters between patients with infection, experimentally challenged individuals and vaccine-induced immunity.

• WP 3: Clinical trials to identify the differences in immune response profiles to aP and wP vaccines in selected population cohorts and gain mechanistic insights into mediators of protection

  In WP3 we will investigate vaccine-induced immunity, with a focus on comparison between aPs and wPs. Although both aPs and wPs protect against disease, wPs have been shown to induce more persistent immunity. We will therefore perform a number of randomized clinical trials (RCTs), both in Europe as well as in The Gambia, to investigate the immediate and long- term immune responses to primary vaccination with aP versus wP in infants.

• WP 4: Interaction with Regulatory Authorities and Public Health Institutes

  In WP4 we focus on regulatory issues. The overall objective is to ensure early involvement and the acceptance of novel immunoassays and biomarkers of protection by regulatory authorities.

• WP 5: Clinical trial assays and biomarker discovery platforms; Biobanking, database management and bioinformatics for the identification of biomarkers

  WP5A serves as a central hub for the laboratory analysis of biological samples obtained from WP1-3 (WP5A) and provides the core bioinformatic pipeline (WP5B) to analyze complex data sets needed for biomarkers discovery.

  In WP5B, we will perform the data analyses that will permit us to identify, from the molecular, cellular and immunological data from WP1, WP2 and WP3, which immunological readouts yield biomarkers for protection against colonisation/disease and for the persistence of immunity. We will process, store and manage the data and make them accessible to the consortium. Additionally, we will use systems biology tools and computational modelling to identify specific biomarkers of protection and explore the correlation structure of the data to develop a mechanistic understanding of pertussis immunity and interpret the biomarkers. Finally, biological samples will be stored in a central biobank to allow replication measurements of biomarkers, and possibly testing with additional readouts.

• WP 6: Project Coordination and Management

  In WP6, we will cover all aspects of project governance, management and coordination of PERISCOPE.

• WP 7: Communication, dissemination and training activities

  In WP7, we will coordinate the communication strategy and dissemination activities. This involves internal communication within PERISCOPE as well as external communication with other stakeholders and project consortia, including patient organizations, academia and the general public.

PERISCOPE members will establish a dialogue with European regulatory authorities and Public Health Institutions. This will facilitate collaboration with representatives of these bodies on incorporation of our findings into Regulatory Guidance and Public Health guidelines for best use of existing and novel vaccines. This also includes evaluation of immunization in pregnancy in settings where wP vaccination is the standard for infants.