Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Seongman Bae; Jae Hoon Ko; Ju Yeon Choi; Woo Jung Park; So Yun Lim; Jin Young Ahn; Kyoung Ho Song; Kyoung Hwa Lee; Young Goo Song; Yong Chan Kim; Yoon Soo Park; Won Suk Choi; Hye Won Jeong; Shin Woo Kim; Ki Tae Kwon; Eun Suk Kang; Ah Ra Kim; Sundong Jang; Byoungguk Kim; Sung Soon Kim; Hee Chang Jang; Jun Yong Choi; Sung Han Kim; Kyong Ran Peck

doi:10.1016/j.cmi.2022.04.019

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Seongman Bae, Jae Hoon Ko, Ju Yeon Choi, Woo Jung Park, So Yun Lim, Jin Young Ahn, Kyoung Ho Song, Kyoung Hwa Lee, Young Goo Song, Yong Chan Kim, Yoon Soo Park, Won Suk Choi, Hye Won Jeong, Shin Woo Kim, Ki Tae Kwon, Eun Suk Kang, Ah Ra Kim, Sundong Jang, Byoungguk Kim, Sung Soon KimHee Chang Jang, Jun Yong Choi, Sung Han Kim, Kyong Ran Peck

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1390.e1-1390.e7
Journal	Clinical Microbiology and Infection
Volume	28
Issue number	10
DOIs	https://doi.org/10.1016/j.cmi.2022.04.019
Publication status	Published - 2022 Oct

Bibliographical note

Funding Information:
This work was supported by Research Program funded by the Korea Disease Control and Prevention Agency (#2021-ER2601-00) and Samsung Medical Center Grant (#SMO1210321). Participant recruitment and sample collection were done by each institution. Immunologic assays and data analysis were performed in Samsung Medical Center and Korea Disease Control and Prevention Agency.

Publisher Copyright:
© 2022 European Society of Clinical Microbiology and Infectious Diseases

All Science Journal Classification (ASJC) codes

Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmi.2022.04.019

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Bae, S., Ko, J. H., Choi, J. Y., Park, W. J., Lim, S. Y., Ahn, J. Y., Song, K. H., Lee, K. H., Song, Y. G., Chan Kim, Y., Park, Y. S., Choi, W. S., Jeong, H. W., Kim, S. W., Kwon, K. T., Kang, E. S., Kim, A. R., Jang, S., Kim, B., ... Peck, K. R. (2022). Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity. Clinical Microbiology and Infection, 28(10), 1390.e1-1390.e7. https://doi.org/10.1016/j.cmi.2022.04.019

@article{4a3b9609946b4c73b7f1ac6b89fc215d,

title = "Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity",

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.",

author = "Seongman Bae and Ko, {Jae Hoon} and Choi, {Ju Yeon} and Park, {Woo Jung} and Lim, {So Yun} and Ahn, {Jin Young} and Song, {Kyoung Ho} and Lee, {Kyoung Hwa} and Song, {Young Goo} and {Chan Kim}, Yong and Park, {Yoon Soo} and Choi, {Won Suk} and Jeong, {Hye Won} and Kim, {Shin Woo} and Kwon, {Ki Tae} and Kang, {Eun Suk} and Kim, {Ah Ra} and Sundong Jang and Byoungguk Kim and Kim, {Sung Soon} and Jang, {Hee Chang} and Choi, {Jun Yong} and Kim, {Sung Han} and Peck, {Kyong Ran}",

note = "Funding Information: This work was supported by Research Program funded by the Korea Disease Control and Prevention Agency (#2021-ER2601-00) and Samsung Medical Center Grant (#SMO1210321). Participant recruitment and sample collection were done by each institution. Immunologic assays and data analysis were performed in Samsung Medical Center and Korea Disease Control and Prevention Agency. Publisher Copyright: {\textcopyright} 2022 European Society of Clinical Microbiology and Infectious Diseases",

year = "2022",

month = oct,

doi = "10.1016/j.cmi.2022.04.019",

language = "English",

volume = "28",

pages = "1390.e1--1390.e7",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier Limited",

number = "10",

}

Bae, S, Ko, JH, Choi, JY, Park, WJ, Lim, SY, Ahn, JY, Song, KH, Lee, KH, Song, YG, Chan Kim, Y, Park, YS, Choi, WS, Jeong, HW, Kim, SW, Kwon, KT, Kang, ES, Kim, AR, Jang, S, Kim, B, Kim, SS, Jang, HC, Choi, JY, Kim, SH & Peck, KR 2022, 'Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity', Clinical Microbiology and Infection, vol. 28, no. 10, pp. 1390.e1-1390.e7. https://doi.org/10.1016/j.cmi.2022.04.019

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity. / Bae, Seongman; Ko, Jae Hoon; Choi, Ju Yeon et al.

In: Clinical Microbiology and Infection, Vol. 28, No. 10, 10.2022, p. 1390.e1-1390.e7.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

AU - Bae, Seongman

AU - Ko, Jae Hoon

AU - Choi, Ju Yeon

AU - Park, Woo Jung

AU - Lim, So Yun

AU - Ahn, Jin Young

AU - Song, Kyoung Ho

AU - Lee, Kyoung Hwa

AU - Song, Young Goo

AU - Chan Kim, Yong

AU - Park, Yoon Soo

AU - Choi, Won Suk

AU - Jeong, Hye Won

AU - Kim, Shin Woo

AU - Kwon, Ki Tae

AU - Kang, Eun Suk

AU - Kim, Ah Ra

AU - Jang, Sundong

AU - Kim, Byoungguk

AU - Kim, Sung Soon

AU - Jang, Hee Chang

AU - Choi, Jun Yong

AU - Kim, Sung Han

AU - Peck, Kyong Ran

N1 - Funding Information: This work was supported by Research Program funded by the Korea Disease Control and Prevention Agency (#2021-ER2601-00) and Samsung Medical Center Grant (#SMO1210321). Participant recruitment and sample collection were done by each institution. Immunologic assays and data analysis were performed in Samsung Medical Center and Korea Disease Control and Prevention Agency. Publisher Copyright: © 2022 European Society of Clinical Microbiology and Infectious Diseases

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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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U2 - 10.1016/j.cmi.2022.04.019

DO - 10.1016/j.cmi.2022.04.019

M3 - Article

C2 - 35598855

AN - SCOPUS:85134641181

SN - 1198-743X

VL - 28

SP - 1390.e1-1390.e7

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 10

ER -

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Abstract

Bibliographical note

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UN SDGs

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