WP2 - Lead & Concept Production - Work performed since the beginning of the project

Overview work package

To determine which assays are to be employed when evaluating candidate universal influenza vaccines

The initial plan with regard to standardisation of assays between the laboratories of different partners was to agree upon a standardised protocol and to provide internal standards to maintain intra-laboratory compatibility. However, after a number of telephone conferences and reviews of the literature, it became clear that, particularly for the measurement of cell-mediated immune responses (i.e. T-cell responses) by flow cytometry, it would be practically impossible to standardise assays in different laboratories. As the crucial aspect of UNISEC is towards a side-by-side comparison of the immune responses induced by the different vaccines, it was decided to instead designate centralised laboratories to carry out the most important of the assays on clinical samples or a large subset thereof. As the putative correlates of protection for vaccines designed to induce predominantly T-cell responses remain unknown, it was considered important to analyse samples using an approach that would maximise the information generated. To this end, a strategy for the multiparametric FACS analysis of immune responses in PBMC was developed in which cells stimulated with different immunogens are evaluated with regard to the induction of multiple intracellular cytokine responses in CD4+ and CD8+ T-cells.

Standardized experimental conditions

Todefineandteststandardizedexperimentalconditionsconsideringantigendose,vaccinationscheme, routesofadministrationandhowtocompareefficacy of vaccine candidates is critical to the success of the UNISEC project. It was therefore agreed that the amountofantigen,vaccinationschemes,andtimepointsforevaluations of the immune responses and levels of protection achieved were all to be assessed under the agreed optimal conditions. However, this also meant that we decided to avoid excessive overlapping investigations between different laboratories and protocols and only go for comparisons between what had previously been identified as the most optimal protocol of the respective vaccine candidate. This thinking was applied to the questions of amount of antigen to be used, route of administration, and time point for evaluations for each vaccine type. Thus, withintheconsortium,the existing vaccine candidates could be administered intramuscularly, intranasally, sublingually , pulmonary or intradermally, depending on the type of vaccine (protein- or DNA-based or a live AIV infection,) and still be compared at optimal time points, as agreed.

The first 6 months were devoted to carefully establishing a strategy and protocol for running side-by-side experiments in the experimental models. The agreed upon conclusion was a protocol focused on the mouse model as a discriminative first step for selection of vaccine formulation and adjuvant use.

Benchmarks of regulatory pathways and commercialization

Developing new generations of medical products like universal influenza vaccines without appropriate communication with the medical regulatory authorities like the European Medical Agency EMA), is risky. UNISEC realizes that success of its newly developed products depends on close communication with authorities during all different stages of the project. For this reason UNISEC has approached all other EU framework 7 consortia working on the development of new universal influenza vaccines, organized a number of meetings (See WP1, Management and Coordination for details), including a meeting with the Innovative Task Force (ITF) of the EMA on 17 June 2015 and the Vaccine Working Party (VWP) of the EMA on 23 November 2016 in order to present and discuss the new concepts of universal vaccines.

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WP2 28 9 15.pdf
3/9/2016 3:20:20 PM
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wp2. UNISEC poster vaccine candidates new.ppt
4/15/2016 9:10:00 AM