한빛사 논문
Seongman Bae 1, a, Jae-Hoon Ko 2, a, Ju-Yeon Choi 3, a, Woo-Jung Park 3, a, So Yun Lim 1, Jin Young Ahn 4, Kyoung-Ho Song 5, Kyoung Hwa Lee 6, Young Goo Song 6, Yong Chan Kim 7, Yoon Soo Park 7, Won Suk Choi 8, Hye Won Jeong 9, Shin-Woo Kim 10, Ki Tae Kwon 11, Eun-Suk Kang 12, Ah-Ra Kim 3, Sundong Jang 3, Byoungguk Kim 3, Sung Soon Kim 3, Hee-Chang Jang 3, Jun Yong Choi 4, **, Sung-Han Kim 1, *, Kyong Ran Peck 2, ***
1) Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
2) Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
3) National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, South Korea
4) Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
5) Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
6) Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
7) Division of Infectious Disease, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea
8) Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea
9) Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea
10) Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
11) Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea
12) Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
* Corresponding author
a Seongman Bae, Jae-Hoon Ko, Ju-Yeon Choi, and Woo-Jung Park contributed equally to this work.
Abstract
Objectives
We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups.
Methods
We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey.
Results
We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti–receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52–12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03–1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01–3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND50, 2367.74 [95% CI, 1970.03–2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88–2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16–470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND50, 872.01 [95% CI, 685.33–1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78–434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05–296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group.
Discussion
Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.
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