Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS‐CoV‐2 Omicron BA.1 and BA.5 variants

Author:

Lee Beomki12ORCID,Ko Jae‐Hoon3ORCID,Kim Yong Chan4ORCID,Baek Jin Yang35ORCID,Park Yoon Soo4ORCID,Song Kyoung‐Ho6ORCID,Kim Eu Suk6ORCID,Lee Kyoung Hwa7ORCID,Song Young Goo7ORCID,Ahn Jin Young8ORCID,Choi Jun Yong8ORCID,Choi Won Suk9ORCID,Bae Seongman10ORCID,Kim Sung‐Han10ORCID,Jeong Hye Won11ORCID,Lee Young Jae12ORCID,Kim Hye‐Jin12,Choi Ju‐Yeon12ORCID,Kim Byoungguk12ORCID,Kim Shin‐Woo13ORCID,Kwon Ki Tae14ORCID,Peck Kyong Ran3ORCID,Kang Eun‐Suk1ORCID

Affiliation:

1. Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

2. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon South Korea

3. Division of Infectious Diseases, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

4. Division of Infectious Diseases, Department of Internal Medicine Yongin Severance Hospital, Yonsei University College of Medicine Yongin South Korea

5. Asia Pacific Foundation for Infectious Diseases (APFID) Seoul South Korea

6. Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine Seongnam South Korea

7. Division of Infectious Diseases, Department of Internal Medicine Gangnam Severance Hospital, Yonsei University College of Medicine Seoul South Korea

8. Department of Internal Medicine Severance Hospital, Yonsei University College of Medicine Seoul South Korea

9. Division of Infectious Diseases, Department of Internal Medicine Korea University Ansan Hospital, Korea University College of Medicine Ansan South Korea

10. Department of Infectious Diseases, Asan Medical Center University of Ulsan College of Medicine Seoul South Korea

11. Department of Internal Medicine Chungbuk National University College of Medicine Cheongju South Korea

12. Division of Vaccine Clinical Research, Center for Vaccine Research National Institute of Infectious Diseases, Korea National Institute of Health Cheongju South Korea

13. Department of Internal Medicine, School of Medicine Kyungpook National University Daegu South Korea

14. Division of Infectious Diseases, Department of Internal Medicine Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Daegu South Korea

Abstract

AbstractDeveloping new antibody assays for emerging SARS‐CoV‐2 variants is challenging. SARS‐CoV‐2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT‐positive sera, we noticed that log‐transformed optical density (OD) ratio of wild‐type (WT) sVNT exhibited better titer‐correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer‐correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false‐negative rates (cPass‐BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F‐BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed‐effects model suggested superior titer‐correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Publisher

Wiley

Subject

Infectious Diseases,Virology

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