Why and how do we harmonise assessment of COVID-19 vaccine trials?

As a result of the world's rapid and collaborative response to the COVID-19 pandemic, over 320 COVID-19 vaccine candidates are now in development — with forty-one already in clinical trials.

To minimise variation in assessment and allow for head-to-head comparisons between promising COVID-19 vaccine candidates, CEPI has launched a new centralised lab network, open to all COVID-19 vaccine developers (CEPI-funded and other), to standardise the evaluation of COVID-19 vaccine candidates and allow for researchers to identify the most successful potential vaccines.

We spoke to Valentina Bernasconi, Preclinical and Immunology Scientist in CEPI's Vaccine R&D Team and Project Leader of the Centralised Laboratory Network, about the role of biological standardisation in vaccine development, CEPI's work within this area, and how the new global lab network will operate:

There's promising data emerging from COVID-19 vaccine trials, but we aren't able to directly compare results. Why is this?

As we have seen with the publication of Phase I trial results from CEPI's COVID-19 vaccine development partners, University of Oxford, Novavax, and Moderna, among others, encouraging data is now emerging on multiple COVID-19 vaccine candidates.

While we should all recognise that there is still a long way to go in terms of vaccine development, this is positive news. However, we currently can't directly compare results and select the most promising vaccine candidates as different laboratories are using different measurements to test if the immune response (e.g., the production of antibodies and/or T-cells) is induced in response to a vaccine dose.

Through centralising the analysis of samples obtained from trials (preclinical, Phase I and Phase II) of COVID-19 vaccine candidates, CEPI's new centralised lab network aims to reduce the risk of interlaboratory variation, which may otherwise arise due to the technical differences when carrying out independent lab analyses.

The samples will instead be tested a group of laboratories using the same methods and the same key reagents (i.e., substances used to carry out a laboratory test), allowing us to draw head-to-head comparisons on multiple vaccine candidates and identify which vaccines may be performing better in these clinical trials.
 

Who is part of the centralised lab network?

The centralised network is a global consortium of testing laboratories which today includes Nexelis (Canada) and Public Health England (PHE, UK), VisMederi Srl (Italy), Viroclinics-DDL (The Netherlands), icddr,b (formerly International Centre for Diarrhoeal Disease Research, Bangladesh), and Translational Health Sciences and Technological Institute (THSTI, India). Nexelis and PHE Porton Down have spearheaded the programme through sharing their advanced testing methodologies and key reagents with the other lab partners. Additional laboratories are due to join soon.

The labs applied to a Call for Proposals that we put out earlier this year and were selected based on their quality system, their capacity to perform the required tests, their ability to work internationally with other labs to use common protocols (the same methodologies), and their record of receiving and handling samples from multiple geographical locations, among other criteria.

We selected a number of labs to be part of this effort as, with over 320 COVID-19 vaccines in development, an individual lab would not have had the capacity to reliably assess the immunogenicity of multiple COVID-19 vaccine candidates. Plus, our global network will make it easier for shipping of samples (i.e., COVID-19 vaccine developers can ship their preclinical and clinical samples to their nearest laboratory knowing it's all going to be assessed under the same methodology).

CEPI has also recently extended our Call for Proposals to also assess Phase III clinical trial samples as part of the centralised lab network. The new Call is open to any laboratory worldwide until 4 October 2020. You can find out more and apply to this Call here.

How will the laboratories follow the same methodology?

To make sure the multiple labs have comparable ways of performing their assessments, all will follow the same protocol and use the same key reagents to analyse samples.

We can think of this effort like teaching multiple cooks around the world to follow the same recipe — without help, chefs may make the same dish in different ways, buy ingredients from different shops and use different brands, meaning the resulting meal will not be the same. By asking everyone to follow the exact ingredient list and exact recipe we can make sure the same meal is created around the world. Our centralised lab network works in much the same way to ensure harmony and standardisation.

CEPI picked the tests (the assays) for COVID-19 at the most advanced stage of development, developed by Nexelis in Canada and Public Health England Porton Down in the UK. The different tests include ELISA (enzyme-linked immunosorbent assay) and pseudo neutralisation assays, provided by Nexelis, and wild-type neutralisation, delivered by PHE Porton Down, and ELISPOT to allow us to evaluate the serological (based on antibodies) and cellular (based on T cells) immune responses elicited by different vaccine candidates. The higher and more specific the immune response is, the more likely the vaccine will be able to protect the vaccinated person against virus infection. Plus, Nexelis and PHE are also supplying critical testing reagents along with controls to ensure results provided by different labs are comparable across the network.

The assay methodologies were shared by Nexelis and PHE Porton Down with the partner labs and we asked Nexelis and PHE to teach the others how to perform the sample analysis. As part of this laboratory-training stage, we asked the network to analyse a set of standard samples to check that assessments are performed in the same way across all labs. This will be repeated every 6 months to check that performance is maintained over time.

How does CEPI's centralised lab network aid COVID-19 vaccine development?

CEPI currently has a diverse COVID-19 vaccine portfolio—the world's largest—of nine COVID-19 vaccine candidates. We're also actively looking to expand our investments in further vaccine candidates to increase the chances of finding a successful vaccine and, alongside Gavi and the World Health Organization (WHO) as part of COVAX, meet our goal to develop, manufacture and equitably deliver up to 2 billion doses of vaccine by the end of 2021.

To help meet this goal, data obtained on the immunogenicity of vaccines will be used to inform and advance CEPI's COVID-19 vaccine portfolio by providing quick and accurate evaluation of our candidate vaccines. And we also wanted to ensure this service was accessible to all, regardless of size, so any COVID-19 vaccine developer can use the network to obtain data which can later help developers and regulators get a more accurate picture of which vaccine candidates have the best safety and immunogenicity profiles.

We are now exploring the possibility of extending the testing to also include Phase III trial samples, as results produced in later-stage efficacy studies help the decision-making process of which COVID-19 vaccine/s shall be brought to licensure.

Have there been efforts like this to create a universal lab for other diseases?

Similar efforts have been conducted and are currently ongoing for clinical testing of HIV and influenza vaccines, with some countries testing samples in centralised national laboratories.

There are also other collaborative efforts taking place around the world to centralise the assessment of COVID-19 vaccine candidates. For example, a similar effort is being taken forward by US NIH which will serve sample testing for US national vaccine developers. CEPI is in regular discussions with US NIH and its partners to ensure our efforts are in alignment.

We believe our collaborative effort to be the first time a project like this has been implemented at such speed and scale. With laboratories situated across Europe, Asia and North America, this is the most globally distributed network, which, through sharing tools and protocols, acts as though we are all working under one roof.

How else is CEPI supporting work to create international standards for the assessment of vaccines?

In addition to COVID-19, CEPI has been working on the development of standards and assays through a Working Group of experts and a series of pathogen-specific Task Forces to address the major needs each for Lassa virus, Nipah virus, Rift Valley Fever and MERS-CoV Standards and Assays.
 

How can non-CEPI funded COVID-19 vaccine developers access the centralised lab network to assess their samples?

All COVID-19 vaccine developers are invited to apply to use CEPI's centralised laboratory network. Through this new network, up to the limit of programme funding, eligible COVID-19 vaccine developers (both CEPI-funded and non-CEPI funded developers) can use the laboratories, without per sample charges, to analyse the immune response elicited by their COVID-19 vaccine candidates in preclinical, Phase I and Phase IIa studies. The number of samples available for testing per developer may be limited depending on response.

Certain commitments may be required for eligibility, such as making timely publication of sample testing results and sharing data that will be produced on the immunogenicity of COVID-19 vaccine candidates to facilitate future regulatory decisions.

In order to monitor interest and adjust the testing capacity, we are requesting that all vaccine developers complete this short survey.

For any COVID-19 vaccine developer ready to submit their samples to CEPI's centralised laboratory network, please complete our Sample Analysis Request Form.

If you have any questions or would like further information, please email us at [email protected]