Evaluating Humoral Immunity against SARS-CoV-2: Validation of a Plaque-Reduction Neutralization Test and a Multilaboratory Comparison of Conventional and Surrogate Neutralization Assays
Emelissa J. Valcourt, Kathy Manguiat, Alyssia Robinson, Yi-Chan Lin, Kento T. Abe, Samira Mubareka, Altynay Shigayeva, Zoë Zhong, Roxie C. Girardin, Alan DuPuis, Anne Payne, Kathleen McDonough, Zhen Wang, Romain Gasser, Annemarie Laumaea, Mehdi Benlarbi, Jonathan Richard, Jérémie Prévost, Sai Priya Anand, Kristina Dimitrova, Clark Phillipson, David H. Evans, Allison McGeer, Anne-Claude Gingras, Chen Liang, Martin Petric, Inna Sekirov, Muhammad Morshed, Andrés Finzi, Michael Drebot, Heidi Wood
Abstract
SARS-CoV-2, the causal agent of COVID-19, has infected over 246 million people and led to over 5 million deaths as of October 2021. With the approval of several efficacious COVID-19 vaccines, methods to evaluate protective immune responses will be crucial for the understanding of long-term immunity in the rapidly growing vaccinated population. The PRNT, which quantifies SARS-CoV-2-neutralizing antibodies, is used widely as a reference standard to validate new platforms but has not undergone substantial validation to ensure excellent inter- and intraassay precision and specificity. Our work is significant, as it describes the thorough validation of a PRNT, which we then used as a reference standard for the comparison of several alternative serological methods to measure SARS-CoV-2-neutralizing antibodies. These assays demonstrated excellent agreement with the reference-standard PRNT and include high-throughput platforms, which can greatly enhance capacity to assess both natural and vaccine-induced protective immunity against SARS-CoV-2.