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Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea

 Eliel Nham  ;  Jae-Hoon Ko  ;  Kyoung-Ho Song  ;  Ju-Yeon Choi  ;  Eu Suk Kim  ;  Hye-Jin Kim  ;  Byoungguk Kim  ;  Hee-Young Lim  ;  Kyung-Chang Kim  ;  Hee-Chang Jang  ;  Kyoung Hwa Lee  ;  Young Goo Song  ;  Yae Jee Baek  ;  Jin Young Ahn  ;  Jun Yong Choi  ;  Yong Chan Kim  ;  Yoon Soo Park  ;  Won Suk Choi  ;  Seongman Bae  ;  Sung-Han Kim  ;  Eun-Suk Kang  ;  Hye Won Jeong  ;  Shin-Woo Kim  ;  Ki Tae Kwon  ;  Sung Soon Kim  ;  Kyong Ran Peck 
 FRONTIERS IN IMMUNOLOGY, Vol.13 : 968105, 2022-09 
Journal Title
Issue Date
Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19 Vaccines ; COVID-19* / prevention & control ; COVID-19* / therapy ; Cohort Studies ; Humans ; Immunization, Passive ; Kinetics ; Pandemics ; Prospective Studies ; Republic of Korea / epidemiology ; SARS-CoV-2 ; Vaccination ; Viral Vaccines*
COVID-19 ; SARS-CoV-2 ; neutralizing antibody ; protective immunity ; vaccination
Introduction: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.

Methods: We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant.

Results: We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).

Conclusion: Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yong Chan(김용찬)
Park, Yoon Soo(박윤수)
Baek, Yae Jee(백예지)
Song, Young Goo(송영구) ORCID logo https://orcid.org/0000-0002-0733-4156
Ahn, Jin Young(안진영) ORCID logo https://orcid.org/0000-0002-3740-2826
Lee, Kyoung Hwa(이경화) ORCID logo https://orcid.org/0000-0003-0033-1398
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
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