The Story Behind How PPD® Laboratory Services Created a Method to Compare COVID-19 Vaccine Candidates

Marie E. Bonhomme, Ph.D. (director of immunology, PPD^® Laboratory services, vaccine sciences lab), explains how scientists created an international standard to test the efficacy of COVID-19 vaccine candidates.

As early as April 2020, drug developers were racing to create and test the efficacy of COVID-19 vaccines. There were hundreds of candidates, but one major gap: There was no standard to grade vaccine effectiveness. While methods to evaluate potential vaccines existed, COVID-19 vaccine candidates could not be readily compared without taking extra, time-consuming steps.

Scientists from PPD Laboratory services stepped in to find a solution. They calibrated assays to a single international standard to express efficacy in relative terms. Assay calibration and quantitative comparison can be easily accomplished, enabling researchers to discuss vaccine candidate effectiveness in relative terms.

That research was recently published in the peer-reviewed journal PlosOne. While the approach is novel and new, it has the potential to become a new standard in the way scientists, drug developers and researchers express COVID-19 vaccine assay efficacy. This infographic summarizes the research findings.

The Problem with Traditional Assay Benchmarking

There is no straightforward way to benchmark immunogenic responses – and that’s a problem when comparing the effectiveness of candidate vaccines.

Traditional methods to evaluate candidate vaccines are often complex because they must assess precision, accuracy, dilutional linearity, selectivity and specificity, and it takes time to make those determinations. Moreover, the test results may be expressed differently for various vaccine candidates because there is no single accepted standard.

PPD’s approach streamlines and simplifies the process so that vaccine efficacy can be easily compared with fewer steps and drug developers can make decisions more efficiently.

Comparing Efficacy Across COVID-19 Vaccine Candidates

The emergence of COVID in late 2019 led to a massive international effort as scientists worked to develop vaccine candidates that were effective against the virus. By the end of 2020, more than 60 possible COVID vaccines were in clinical trials, and more than 170 were in preclinical development.

Both the World Health Organization (WHO) and the U.S. Food and Drug Administration (FDA) published guidance on how each immune response should be evaluated from humoral, cellular and functional perspectives. However, there was not one recommended or standardized method for doing so.

• The WHO vaccine guidance said that the serologic correlates of protection evaluated must be justified and supported by the best scientific evidence available. They also suggested that there should be evidence of assay validation and standardization.
• FDA guidance was similar, saying that assays utilized to evaluate immunogenicity should demonstrate suitability for their intended purposes and be validated before use in pivotal clinical trials.

Neither guidance provided a relative bar for vaccine effectiveness.

Easier and Effective Vaccine Candidate Bridging

The process to develop COVID-19 vaccines underscored the fact that if researchers could easily compare the efficacy of candidate vaccines using a common language, this simplified bridging could accelerate the vaccine development process.

“Comparing the effectiveness of vaccine candidates is difficult and time-intensive, so at the onset of the pandemic, we quickly set out to find an alternative approach that would be more efficient,” said Marie E. Bonhomme, Ph.D., director of immunology, PPD Laboratory services, vaccines sciences lab. “My colleagues and I used an international standard to calibrate our assays, and it greatly simplified the analysis of SARS-CoV-2 vaccines.

“The process is straightforward and can be applied to many situations where a benchmark for immunogenic response isn’t available.”

Determining Vaccine Efficacy with Standardized Assays

Essentially, calibrating assays to international standards compares vaccines candidates like to like. This allows immunogenicity results from different assays or laboratories to be analyzed in relative terms.

Dr. Bonhomme and her team used the WHO’s reference standard to report immunogenicity data in international units. This simple approach to standardization makes it easy to compare immune responses of vaccine candidates or different vaccination regimens.

Expressing the effectiveness of vaccine assays using a common unit of measurement has several far-reaching benefits, including:

• Guiding drug developers as to which vaccine candidates to pursue. Using COVID-19 as an example, the ability to leverage relative terms simplifies how to compare effectiveness and identify candidates worth developing, especially in cases where there are several potential vaccines or regimens.
• Resolving the issue of how to quantify and qualify candidates in cases where there is no immunogenic benchmark for efficacy.

Our laboratory services have a long history of surpassing the status quo in vaccine development. Our expertise and excellence have enabled our vaccine developers to stand at the forefront of new immunogenic methodologies and approaches for decades, and this new research is no exception.

Check out the full article describing this research in PlosOne or download the article summary.