FLUCOP · Standardization and Development of Assays for Assessment of Influenza Vaccines Correlates of Protection

Background: Influenza viruses cause annual epidemic and occasional pandemics, both of which induce significant morbidity and mortality. Influenza infections affect all age groups but children and adults over the age of 65 are at most risk of developing severe disease.Vaccination is the most effective approach to reduce the impact of annual influenza outbreaks and potential pandemics, however, the currently criteria of correlates of protection(CoP) show limitations in predicting protection for seasonal and pandemic vaccines. The Haemagglutinin Inhibition(HAI) antibody titre is the most widely used CoP for seasonal influenza vaccine even if there is a lack of standardisation for conducting HAI and other serological assays and therefore results obtained from different laboratories are not comparable. This leads to the urgent need of improving international standardisation of serological assays to reduce inter laboratory variability and to generate supportive immunological assays to be used in studies aimed at developing clinically relevant surrogate markers of protection of influenza vaccines.Objectives: The main long-term aim of the FLUCOP project is to improve and standardize the existing immunological assays and to develop new assays for the better evaluation of the CoP of influenza vaccines.Main specific FLUCOP objectives include:-achieve standardization of HAI and Virus Neutralization(VN) assays;-promote the understanding and application of Cell-Mediated Immunity (CMI) and Neuraminidase (NA) assays as tools for the evaluation of influenza vaccines; -develop selective new assays which might potentially used for future clinical trials for influenza seasonal vaccine evaluationFLUCOP Consortium and Project Impact: The FLUCOP consortium brings together 26 groups from 7 European countries, and includes contributors from the academic, governmental, non-for-profit and pharmaceutical sectors. As a whole, the consortium has a balanced array of expertise and each group has been carefully selected to avoid overlaps in research activities and to collectively address the planned objectives. FLUCOP is expected to have a significant impact to improve and standardize the existing immunological assays and develop new assays to better evaluate influenza vaccines. This will contribute to the future clinical trial evaluation and possible establishment of correlates of protection Through a public-private collaboration FLUCOP will reach a common agreement on assays and methods to be used by all groups both from the public and private sector for testing influenza vaccines in humans. These efforts are expected to aid evolution of the regulatory guidelines and the practice of the pharmaceutical industry following the application of the methods to efficacy studies.Project plan: To reach the proposed objectives, the FLUCOP project is composed of five focused interconnected work packages(WP).WP1:Standardization of HAI and VN assays.Objective: HAI and VN assays are commonly used to quantify influenza specific antibodies but they show to be highly variable between laboratories. Moreover different protocols are in use in different laboratories, which may contribute to the variability of the assays. This WP aims to improve the standardization and harmonization of these assays and also preparation and qualification of critical reagents.Methodology: Adult and paediatric pre and post influenza vaccination serum samples will be available to consortium partners who are recognized as leading experts in serological analysis of influenza vaccine responses. A target protocol profile will be developed jointly and statistically powdered studies will be design to compare, screen and evaluate consensus protocols. Sera will be analyzed in iterative rounds of testing of the empirically selected consensus protocols and assay conditions. A final data driven consensus protocol(s) for each HAI and VN format will agreed upon, based on the results o