Kuan Ting Liu

All Publications

• Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines. Microbes and infection Kung, Y. A., Huang, S. Y., Huang, C. G., Liu, K. T., Huang, P. N., Yu, K. Y., Yang, S. L., Chen, C. P., Cheng, C. Y., Lee, I. K., Lin, S. M., Chang, H. P., Lin, Y. T., Liu, Y. C., Chen, G. W., Shih, S. R. 2023; 25 (1-2): 105044

  Abstract

  The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

  View details for DOI 10.1016/j.micinf.2022.105044

  View details for PubMedID 36096357

  View details for PubMedCentralID PMC9461341

• Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody. Viruses Liu, K. T., Han, Y. J., Wu, G. H., Huang, K. A., Huang, P. N. 2022; 14 (7)

  Abstract

  We aimed to review the existing literature on the different types of neutralization assays and international standards for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We comprehensively summarized the serological assays for detecting neutralizing antibodies against SARS-CoV-2 and demonstrated the importance of an international standard for calibrating the measurement of neutralizing antibodies. Following the coronavirus disease outbreak in December 2019, there was an urgent demand to detect neutralizing antibodies in patients or vaccinated people to monitor disease outcomes and determine vaccine efficacy. Therefore, many approaches were developed to detect neutralizing antibodies against SARS-CoV-2, such as microneutralization assay, SARS-CoV-2 pseudotype virus assay, enzyme-linked immunosorbent assay (ELISA), and rapid lateral flow assay. Given the many types of serological assays for quantifying the neutralizing antibody titer, the comparison of different assay results is a challenge. In 2020, the World Health Organization proposed the first international standard as a common unit to define neutralizing antibody titer and antibody responses against SARS-CoV-2. These standards are useful for comparing the results of different assays and laboratories.

  View details for DOI 10.3390/v14071560

  View details for PubMedID 35891540

  View details for PubMedCentralID PMC9322699

• Quantifying Neutralizing Antibodies in Patients with COVID-19 by a Two-Variable Generalized Additive Model. mSphere Liu, K. T., Gong, Y. N., Huang, C. G., Huang, P. N., Yu, K. Y., Lee, H. C., Lee, S. C., Chiang, H. J., Kung, Y. A., Lin, Y. T., Hsiao, M. J., Huang, P. W., Huang, S. Y., Wu, H. T., Wu, C. C., Kuo, R. L., Chen, K. F., Hung, C. T., Oguntuyo, K. Y., Stevens, C. S., Kowdle, S., Chiu, H. P., Lee, B., Chen, G. W., Shih, S. R. 2022; 7 (1): e0088321

  Abstract

  Considering the urgent demand for faster methods to quantify neutralizing antibody titers in patients with coronavirus (CoV) disease 2019 (COVID-19), developing an analytical model or method to replace the conventional virus neutralization test (NT) is essential. Moreover, a "COVID-19 immunity passport" is currently being proposed as a certification for people who travel internationally. Therefore, an enzyme-linked immunosorbent assay (ELISA) was designed to detect severe acute respiratory syndrome CoV 2 (SARS-CoV-2)-neutralizing antibodies in serum, which is based on the binding affinity of SARS-CoV-2 viral spike protein 1 (S1) and the viral spike protein receptor-binding domain (RBD) to antibodies. The RBD is considered the major binding region of neutralizing antibodies. Furthermore, S1 covers the RBD and several other regions, which are also important for neutralizing antibody binding. In this study, we assessed 144 clinical specimens, including those from patients with PCR-confirmed SARS-CoV-2 infections and healthy donors, using both the NT and ELISA. The ELISA results analyzed by spline regression and the two-variable generalized additive model precisely reflected the NT value, and the correlation between predicted and actual NT values was as high as 0.917. Therefore, our method serves as a surrogate to quantify neutralizing antibody titer. The analytic method and platform used in this study present a new perspective for serological testing of SARS-CoV-2 infection and have clinical potential to assess vaccine efficacy. IMPORTANCE Herein, we present a new approach for serological testing for SARS-CoV-2 antibodies using innovative laboratory methods that demonstrate a combination of biology and mathematics. The traditional virus neutralization test is the gold standard method; however, it is time-consuming and poses a risk to medical personnel. Thus, there is a demand for methods that rapidly quantify neutralizing antibody titers in patients with COVID-19 or examine vaccine efficacy at a biosafety level 2 containment facility. Therefore, we used a two-variable generalized additive model to analyze the results of the enzyme-linked immunosorbent assay and found the method to serve as a surrogate to quantify neutralizing antibody titers. This methodology has potential for clinical use in assessing vaccine efficacy.

  View details for DOI 10.1128/msphere.00883-21

  View details for PubMedID 35107336

  View details for PubMedCentralID PMC8809379