The CEPI centralised laboratory network: supporting COVID-19 vaccine development.

With a wide range of COVID-19 vaccine development platforms and extensive variability between laboratory assays, comparison of results for vaccine trials can be challenging. The Coalition for Epidemic Preparedness Innovations (CEPI) has established a global network of laboratories to centralise testing and enable comparison of immunological responses generated by COVID-19 vaccines. The CEPI centralised laboratory network aims to enable key immunogenicity and efficacy endpoint evaluation, support COVID-19 vaccine developers in the pathway towards licensure, and help the identification of immune correlates of protection.

The selection of participating laboratories was carried out through two public requests for proposals. Applicants were evaluated on their technological expertise, successful track record of supporting clinical trials, appropriate quality system, and ability to work internationally to harmonise assay protocols. The laboratories currently included in the CEPI centralised laboratory network2, 3, 4 are Nexelis, Public Health England, VisMederi, Viroclinics–DDL, International Centre for Diarrhoeal Disease Research Bangladesh, Translational Health Sciences and Technological Institute, UK National Institute for Biological Standards and Control, Q2 Solutions, and Universidad Nacional Autónoma de México (for geographical locations see appendix).

Six qualified assays were included to evaluate humoral and cellular immune responses after vaccination. The humoral response analysis includes the evaluation of binding and neutralising antibodies. The prefusion spike protein and receptor-binding domain ELISA were used to quantify anti-SARS-CoV-2 IgG antibodies in sera to the most common targets used in vaccine formulations. The nucleocapsid ELISA can be used to measure responses to immunisation with both whole virus vaccines and SARS-CoV-2 infection. The wild-type virus neutralisation assay (VNA) and the pseudovirus neutralising assay (PNA) measure virus-specific neutralising antibodies in serum samples. VNA targets the original SARS-CoV-2 Victoria/1/2020 (subsequently renamed BetaCoV/Australia/VIC01/2020) strain and requires biosafety level 3 facilities, whereas PNA allows determination of neutralisation activity in a standard biosafety level 2 laboratory. The ELISAs and the neutralisation assays are standardised to the WHO International Standard for anti-SARS-CoV-2 immunoglobulin developed by the National Institute for Biological Standards and Control, which will allow harmonisation of data produced in laboratories around the globe. Cell-mediated immunity is measured by the enzyme-linked immunospot (ELISpot) assay, which detects production of interferon-γ and interleukin-5 to SARS-CoV-2 spike protein peptides. CEPI is currently focusing on expanding to analysis of samples against the most relevant variants of concern.

The mentioned assays were developed and qualified by Public Health England (VNA) and Nexelis (ELISA, PNA, and ELISpot); validation is in progress. All assays are in the process of technology transfer to the other participating laboratories using common standardised operating procedures, the same key reagents, and standardised controls and acceptance criteria to ensure that all laboratories are generating concordant results.

The CEPI centralised laboratory network is a global resource, committed to provide testing support to all COVID-19 vaccine developers to facilitate standardised measurement of immune responses to vaccines. A global footprint reduces sample shipment challenges. We have so far received sample analysis requests from 60 vaccine developers and, with the endorsement from regulators, we encourage all others to use this harmonised approach.