Leading the Way to Develop Reference Assays for COVID-19 Vaccines

Advanced Assays and Expertise for SARS-CoV-2 Research

In January 2020, Nexelis, a Q² Solutions Company, initiated work on SARS-CoV-2 to rapidly support the global pandemic response. In partnership with UK Health Security Agency (UKHSA), Nexelis’ leading scientists developed in vivo models; expressed, purified, and characterized viral proteins; and designed viral and surrogate pseudovirion neutralization assays (PNA). Our team produced assays measuring humoral and cellular response to SARS-CoV-2 and its variants to evaluate vaccines and antivirals in all phases, from lead optimization to preclinical through large-scale, advanced clinical.

To date, we initiated collaborations and agreements with the leading large pharma and biotech companies around the world for in vivo, preclinical, and clinical development of:

  • mRNA vaccine
  • DNA plasmid vaccine
  • Live attenuated vaccine
  • Non-replicating viral vector
  • Protein subunit
  • Therapeutic and prophylactic antibodies
  • Antivirals marketed for other indications

Modification of the VSV Virus

Pseudotyped Virus Production

Pseudotyped Neutralization Assay

Winner 2022 ViE Best Central/Specialty Laboratory

Recognition for Reference Assay Development in the COVID-19 Field

  • Bill & Melinda Gates Foundation (BMGF) reference lab for all grantees
  • The Coalition for Epidemic Preparedness (CEPI) referral lab for humoral and cellular testing
  • World Health Organization (WHO) public statement signatory for collaboration on COVID-19
  • UK Health Security Agency strategic partner
  • Coronavirus Immunotherapy Consortium for Antibody-Based Therapies (CoVIC) partner
  • Biomedical Advanced Research and Development Authority (BARDA)/Operation Warp Speed COVID-19 Medical Countermeasure Support Service Partner for high-throughput SARS-COV-2 assay development and testing

COVID-19: Timeline of Events

Nexelis and UKHSA played a determinant role in the struggle against SARS-Cov-2, partnering with multiple multinational pharmaceutical companies, innovative biotechnology companies, governmental and nongovernmental bodies including BMGF, CEPI, and BARDA. We developed reference vaccine and drug efficacy assessment assays and transferred their technology to a network of clinical testing laboratories all over the world.

During these 18 months, Nexelis and UKHSA supported more than 60 COVID-19-related development projects and testing of more than 50,000 samples per month in BSL-2 and BSL-3 laboratories.

Timeline of Events & Contributions in the fight against COVID-19

December 2019
Wuhan Municipal Health Commission, China, reports a cluster of cases of pneumonia in Wuhan, Hubei Province. A novel coronavirus, named SARS-CoV-2, was eventually identified.
January 2020

WHO Director General declares the novel coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) as of Jan 30, 2020, based on multiple events.

UKHSA receives early information about the upcoming pandemic situation. The SARS-CoV-2 Victoria/1/2020 genetic sequence is publicly released on Jan 12, 2020, and the strain was received at the laboratories of UKHSA, our strategic partner, a few days later.

The strategic partnership in place between Nexelis and UKHSA enables us to understand and prepare for the pandemic earlier than any other commercial entity. Unlike other groups, Nexelis gets a head start planning for the industry’s immediate needs such as sequencing and rtPCR as well as tools to assess drug and vaccine efficacy against the emerging disease.

The situation highlights the competitive advantage of Nexelis’ close relationships with the world’s premier academic teams in the vaccine field.

February 2020

Nexelis and UKHSA discuss R&D avenues and potential vaccine targets. In the race to develop a vaccine, being the commercial leader means starting from scratch with no reagents, constructs or assays available off the shelf.

The overall R&D budget needed exceeds Nexelis’ budgetary allocation, but management decides to initiate:

  • The production of receptor-binding domain (RBD), nucleocapsid (N) and spike antigen (S) asspike proteins viewed by the team as the most probable target
  • The production of lentivirus pseudoparticles due to the shortage in BSL-3 testing capacity globally to overcome a bottleneck in the development of new vaccines
  • The development of animal models (initially hamster, ferret and mouse then rat and pig at a later stage) needed for challenge studies

Nexelis’ decision to initiate SARS-CoV-2 work without even having obtained any kind of client commitment provides the company with a critical timeline advantage, illustrating our ability to move faster than less agile organizations.

March 2020

BMGF sponsors the development of universal preclinical grade assays made available to all their grantees. Based on a successful existing collaboration with Nexelis in the malaria area and discussions with our experts, BMGF decides to entrust Nexelis with this strategic project.

The assays are intended to be developed based on a construct from the Dale and Betty Bumpers Vaccine Research Center (VRC) at the National Institutes of Health (NIH), aiming to facilitate the acceptance of the assays by all stakeholders.

BMGF and CEPI bring about a paradigm shift in the vaccine R&D area that involves more open collaboration and communication between stakeholders. This shift facilitates easy review of universal assays by regulatory bodies and improved access to new medication in developing countries.

Business-wise, it means an evolution in Nexelis’ business model. R&D efforts previously structured on a fee for service basis did not enable Nexelis to keep any IP on the assays developed. R&D assets now remain the property of Nexelis, accessible through an access fee. The decision to proceed with this new model took in less than a week — another demonstration of Nexelis’ superior agility.

The change in model increases barriers to entry into the vaccine bioanalytical field and a consolidating factor around a couple of leading players.

April 2020

Nexelis joins WHO’s prestigious signatory list of key opinion leaders working to accelerate the development of safe and effective vaccines for SARS-COV-2.

Nexelis, with its strong credentials in Protein Sciences, quickly switch to a VSVΔG-luciferase format from the previous low yielding lentivirus pseudoparticle generation system. The production issue faced by Nexelis might have been a project killer for a CRO with weaker credentials in the field of protein sciences. The quick adoption of a new production system showcases the strategic importance of Nexelis’ same-site clinical testing teams (such as the protein sciences team), a unique function of Nexelis.

BMGF extends its project scope to pseudoparticles neutralization assay, Spike ELISA, RBD ELISA, nucleocapsid ELISA, ELISpot IFN-g, ICS, spike ELISA – IgA, qPCR, and designates Nexelis as its referral laboratory. No other CRO in the world would have the capacity to develop and high-throughput test so many later-stage assays.

May 2020

A first Phase I/II clinical testing assignment is executed, outside the BMGF agreement, for an international pharmaceutical company’s vaccine, which was among the first group to reach the commercial stage.

June 2020

Nexelis participates in a SARS-CoV-2 Neutralizing Assay Concordance Survey (SNACS) panel testing comparing the results of 48 reference laboratories around the globe (18 using a wild-type assay and 30 a PNA method). The results demonstrate the excellent precision and accuracy of Nexelis’ assays and shows our PNA assay to be among the best in class. The outcomes of the survey are widely distributed to the scientific community by lead investigator David Montefiori from Duke Human Vaccine Institute (DHVI).

Nexelis’ PNA method surpassed the wild-type methods, which is the industry gold standard, in precision and accuracy, and the results showed our PNA method was more robust than most of the wild-type assays run in a BSL-3 environment. Further evidence to support acceptance by regulatory bodies. As PNA assays can be performed in a high-throughput BSL-2 environment, we were able to solve a good portion of the industrial issue of a world shortage in BSL-3 testing capacity.

August 2020

CEPI partners with Nexelis, asking us to provide a fully validated clinical version of the assays developed with BMGF support and to produce reagents needed for future clinical testing purposes.

The agreement includes a technology transfer of various ELISAs as well as PNA and VNA assays from Nexelis and PHE to several global laboratories selected by CEPI based on critical reagents produced by Nexelis in Laval.

Consequently, Nexelis has unique technology transfer experience, which will emerge as an increasingly important differentiator in years to come.

Nexelis transfers Spike ELISA and PNA methods developed in Laval to our Seattle facility for a non-human primate (NHP) study, whose samples export from the US would have required a minimum of two months.

Seattle, whose historical core business was in the biomarkers field, successfully adapted promptly to this priority responding to industry needs and initiated infectious diseases activities (ligand binding, neutralization, cell-based assays) for a number of pharmaceutical sponsors and governmental or nongovernmental organizations.

Leveraging the existing scientific skills enabled Nexelis to further enlarge its service offering to sponsors in areas such as cytokines and HIV testing.

The SARS-CoV-2 events happened to be an integration accelerator for Nexelis where our different laboratories joined forces to serve the needs of our clients, including the recently acquired ImmunXperts site in Belgium.  ImmunXperts, a Nexelis company world class immunogenicity science, were leveraged in the development of several of our assays.

October 2020

CEPI announces the creation of a global network of clinical sample testing laboratories to reliably assess and compare the immunological responses generated by SARS-COV-2 vaccine candidates.

The network uses the same testing reagents originating at Nexelis and PHE labs, and each laboratory follows common protocols to measure the immunogenicity of multiple SARS-CoV-2 vaccine candidates (both CEPI-funded and non-CEPI-funded developers).

The laboratories initially selected for this vaccine assessment network were:

  • Nexelis (Canada) and UK Health Security Agency (UKHSA)
  • VisMederi (Italy)
  • Viroclinics-DDL (Netherlands)
  • ICDDR (Bangladesh)
  • THSTI (India)

Since Oct. 2020, additional labs were qualified:

  • Q2 Solutions (U.S.)
  • NIBSC (U.K.)
  • UNAM (Mexico)

Overall, 40 assays are being transferred from Nexelis to the various laboratories.

The initiative from CEPI gives to Nexelis and UKHSA a central, visible role in the deployment of a global harmonized solution in the assessment of SARS-CoV-2 vaccines.

November 2020

Contract executed with BARDA for the testing in Seattle for a 384-well MSD assay to assess binding antibodies for S, RBD and N. The validated assay was transferred from VRC at NIH and validated in Seattle (S-ELISA) to support testing from multiple sponsors being funded by BARDA.

BARDA recognizes Nexelis teams’ expertise and willingness to support a complex project benefiting multiple sponsors. BARDA shared its praise with our team in Seattle stating that they were doing “spectacularly” well – high praise given BARDA’s internal and network of resources.

January 2021

The acquisition of GSK Marburg vaccine development site adds a group of 70 scientists with a 20-year legacy in the virology field under Novartis and GSK management.

March 2021

Nexelis decides to expand its laboratories in Gosselies, Seattle and Laval with the aim to reach a capacity of one million tests per year.

The combination of all our initiatives: a fast ramp-up in Laval (a two-fold capacity increase in one year), a reallocation of our resources on vaccine projects in Seattle and the Marburg acquisition make Nexelis the unquestioned industry segment leader, with a capacity far exceeding other bioanalytical laboratories with a presence in the vaccine area.

Our company partners with CGI to deploy a fully digital solution that will be a determinant component in the development of Nexelis testing capacity.

April 2021

Publication in Nature Protocols by UKHSA and Nexelis teams “Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays publication”

May 2021

The U.K. government pledges £29m more to fast-track vaccines against SARS-CoV-2 variants in Porton Down facilities. The BSL-3 clinical capacity is expected to double by January 2022.

Nexelis decides to initiate the deployment of BSL-3 laboratories to further support SARS-CoV-2 vaccine development. These laboratories will also be used to develop assays supporting vaccine evaluation for re-emerging, resurging or newly emerging diseases.

Validated wild-type neutralization assays will be transferred from UKHSA to Nexelis. Nexelis and UKHSA have supported more than 60 development programs including four out of five vaccines first reaching the commercial stage.

There is a community consensus around two points:

  • Uncertainties about the efficacy of existing vaccines on variants and the duration of their immunological protection make it unrealistic to believe that the SARS-CoV-2 R&D efforts will cease in the short term
  • The world needs to be better prepared for the next pandemic

Nexelis intends to maintain a capacity available to SARS-CoV-2 projects.  Nexelis is in active discussions around initiatives to shorten developmental processes with governmental and nongovernmental organizations.

June 2021

Publication in Nature Communications by members of CoVIC and key Nexelis’ scientists, “COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models” features data generated by our team in Laval, QC.