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Front Immunol. 2022;13:968105.

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.

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제1저자 남엘리엘, 고재훈, 송경호, 최주연 · 교신저자 정혜원, 김신우, 권기태, 김성순, 백경란

PMID 36211416 PMC9538478 DOI 10.3389/fimmu.2022.968105 IF 7 감염내과
소속 (12)
  1. Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  2. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
  3. National Institute of Infectious Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea.
  4. Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
  5. Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
  6. Division of Infectious Disease, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea.
  7. Division of Infectious Diseases, Department of Internal Medicine, Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
  8. Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  9. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  10. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea.
  11. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
  12. Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.

Abstract

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.

Copyright © 2022 Nham, Ko, Song, Choi, Kim, Kim, Kim, Lim, Kim, Jang, Lee, Song, Baek, Ahn, Choi, Kim, Park, Choi, Bae, Kim, Kang, Jeong, Kim, Kwon, Kim and Peck.

Keywords

COVID-19SARS-CoV-2neutralizing antibodyprotective immunityvaccination

Figures

Figure 1
Figure 1 Vaccination schedule and sample acquisition timeline for each group. ChAd, AZD1222 ChAdOx1 vaccine; BNT, BNT162b2 vaccine; PRNT, plaque-reduction neutralizing test.
Figure 2
Figure 2 Measured neutralizing and anti-RBD antibody levels. Measured neutralizing antibody levels of ChAd (A), BNT (B), and ChAd-BNT (C) groups and anti-RBD antibody levels of ChAd (D), BNT (E), and ChAd-BNT (F) groups are depicted. *Because the ChAd-BNT group was enrolled later, the baseline and week 3 antibody levels of the ChAd-BNT group were adopted from the ChAd group. ChAd, AZD1222 ChAdOx1 vaccine; BNT, BNT162b2 vaccine; PRNT, plaque-reduction neutralizing test; ND50, 50% neutralizing dose; RBD, receptor binding domain.
Figure 3
Figure 3 Estimation of protective immunity against WT SARS-CoV-2 for a 26-week period after vaccination. Individual PRNT ND50 values were calculated for each week after the first vaccine dose (transparent color) using the slope between the measured sampling points (dark color) and plotted for each vaccination group [ChAd (A), BNT (B), and ChAd-BNT (C)]. The distributions of PRNT ND50 titers for each week in ChAd (D), BNT (E), and ChAd-BNT (F) groups are presented using three-dimensional graphs. *Because the ChAd-BNT group was enrolled later, the baseline and week 3 antibody levels of the ChAd-BNT group were adopted from the ChAd group. WT, wild-type; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; PRNT, plaque-reduction neutralizing test; ND50, 50% neutralizing dose; ChAd, AZD1222 ChAdOx1 vaccine; BNT, BNT162b2 vaccine.
Figure 4
Figure 4 Estimated protective immunity against the Delta variant using the PRNT correlation equation. A correlation equation between the PRNT ND50 against WT SARS-CoV-2 and that against the Delta variant was deduced using 140 serum samples that underwent PRNT against the two strains simultaneously (A). The PRNT ND50 against the Delta variant was calculated for each measured time point (B), and the PRNT ND50 for each week was estimated using the slope between measured points (C). WT, wild-type; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; PRNT, plaque-reduction neutralizing test; ND50, 50% neutralizing dose; ChAd, AZD1222 ChAdOx1 vaccine; BNT, BNT162b2 vaccine.

그림 출처: PubMed Central 공개 논문 (PMC9538478)

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Frontiers in immunology · eISSN 1664-3224
전자 출판
2022-09-23
MeSH
Antibodies, Neutralizing · Antibodies, Viral · BNT162 Vaccine · COVID-19* / prevention & control / therapy · COVID-19 Vaccines · Cohort Studies · Humans · Immunization, Passive · Kinetics · Pandemics · Prospective Studies · Republic of Korea / epidemiology · SARS-CoV-2 · Vaccination · Viral Vaccines* · COVID-19 Serotherapy
Substances
Antibodies, Neutralizing · Antibodies, Viral · BNT162 Vaccine · COVID-19 Vaccines · Viral Vaccines
참고문헌
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