A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

I. Jung Lee; Cheng Pu Sun; Ping Yi Wu; Yu Hua Lan; I. Hsuan Wang; Wen Chun Liu; Joyce Pei Yi Yuan; Yu Wei Chang; Sheng Che Tseng; Szu I. Tsung; Yu Chi Chou; Monika Kumari; Yin Shiou Lin; Hui Feng Chen; Tsung Yen Chen; Chih Chao Lin; Chi Wen Chiu; Chung Hsuan Hsieh; Cheng Ying Chuang; Chao Min Cheng; Hsiu Ting Lin; Wan Yu Chen; Fu Fei Hsu; Ming Hsiang Hong; Chun Che Liao; Chih Shin Chang; Jian Jong Liang; Hsiu Hua Ma; Ming Tsai Chiang; Hsin Ni Liao; Hui Ying Ko; Liang Yu Chen; Yi An Ko; Pei Yu Yu; Tzu Jing Yang; Po Cheng Chiang; Shang Te Hsu; Yi Ling Lin; Chong Chou Lee; Han Chung Wu; Mi Hua Tao

doi:10.1186/s12929-022-00830-1

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

I. Jung Lee
, Cheng Pu Sun
, Ping Yi Wu
, Yu Hua Lan
, I. Hsuan Wang
, Wen Chun Liu
, Joyce Pei Yi Yuan
, Yu Wei Chang
, Sheng Che Tseng
, Szu I. Tsung
, Yu Chi Chou
, Monika Kumari
, Yin Shiou Lin
, Hui Feng Chen
, Tsung Yen Chen
, Chih Chao Lin
, Chi Wen Chiu
, Chung Hsuan Hsieh
, Cheng Ying Chuang
, Chao Min Cheng

Hsiu Ting Lin, Wan Yu Chen, Fu Fei Hsu, Ming Hsiang Hong, Chun Che Liao, Chih Shin Chang, Jian Jong Liang, Hsiu Hua Ma, Ming Tsai Chiang, Hsin Ni Liao, Hui Ying Ko, Liang Yu Chen, Yi An Ko, Pei Yu Yu, Tzu Jing Yang, Po Cheng Chiang, Shang Te Hsu, Yi Ling Lin, Chong Chou Lee, Han Chung Wu, Mi Hua Tao

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

30 Scopus citations

Abstract

Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods: We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Original language	English
Article number	49
Journal	Journal of Biomedical Science
Volume	29
Issue number	1
DOIs	https://doi.org/10.1186/s12929-022-00830-1
State	Published - Dec 2022
Externally published	Yes

Keywords

Booster dose
COVID-19
Cross-protectivity
Hybrid vaccine
Next generation vaccine
Omicron vaccine
SARS-CoV-2
Variants of concern
mRNA vaccine

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10.1186/s12929-022-00830-1

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Lee, I. J., Sun, C. P., Wu, P. Y., Lan, Y. H., Wang, I. H., Liu, W. C., Yuan, J. P. Y., Chang, Y. W., Tseng, S. C., Tsung, S. I., Chou, Y. C., Kumari, M., Lin, Y. S., Chen, H. F., Chen, T. Y., Lin, C. C., Chiu, C. W., Hsieh, C. H., Chuang, C. Y., ... Tao, M. H. (2022). A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants. Journal of Biomedical Science, 29(1), Article 49. https://doi.org/10.1186/s12929-022-00830-1

@article{8f1114d0ade44c3a943275c90cbe9544,

title = "A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants",

abstract = "Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods: We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In na{\"i}ve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.",

keywords = "Booster dose, COVID-19, Cross-protectivity, Hybrid vaccine, Next generation vaccine, Omicron vaccine, SARS-CoV-2, Variants of concern, mRNA vaccine",

author = "Lee, \{I. Jung\} and Sun, \{Cheng Pu\} and Wu, \{Ping Yi\} and Lan, \{Yu Hua\} and Wang, \{I. Hsuan\} and Liu, \{Wen Chun\} and Yuan, \{Joyce Pei Yi\} and Chang, \{Yu Wei\} and Tseng, \{Sheng Che\} and Tsung, \{Szu I.\} and Chou, \{Yu Chi\} and Monika Kumari and Lin, \{Yin Shiou\} and Chen, \{Hui Feng\} and Chen, \{Tsung Yen\} and Lin, \{Chih Chao\} and Chiu, \{Chi Wen\} and Hsieh, \{Chung Hsuan\} and Chuang, \{Cheng Ying\} and Cheng, \{Chao Min\} and Lin, \{Hsiu Ting\} and Chen, \{Wan Yu\} and Hsu, \{Fu Fei\} and Hong, \{Ming Hsiang\} and Liao, \{Chun Che\} and Chang, \{Chih Shin\} and Liang, \{Jian Jong\} and Ma, \{Hsiu Hua\} and Chiang, \{Ming Tsai\} and Liao, \{Hsin Ni\} and Ko, \{Hui Ying\} and Chen, \{Liang Yu\} and Ko, \{Yi An\} and Yu, \{Pei Yu\} and Yang, \{Tzu Jing\} and Chiang, \{Po Cheng\} and Hsu, \{Shang Te\} and Lin, \{Yi Ling\} and Lee, \{Chong Chou\} and Wu, \{Han Chung\} and Tao, \{Mi Hua\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s12929-022-00830-1",

language = "English",

volume = "29",

journal = "Journal of Biomedical Science",

issn = "1021-7770",

publisher = "BioMed Central Ltd.",

number = "1",

}

Lee, IJ, Sun, CP, Wu, PY, Lan, YH, Wang, IH, Liu, WC, Yuan, JPY, Chang, YW, Tseng, SC, Tsung, SI, Chou, YC, Kumari, M, Lin, YS, Chen, HF, Chen, TY, Lin, CC, Chiu, CW, Hsieh, CH, Chuang, CY, Cheng, CM, Lin, HT, Chen, WY, Hsu, FF, Hong, MH, Liao, CC, Chang, CS, Liang, JJ, Ma, HH, Chiang, MT, Liao, HN, Ko, HY, Chen, LY, Ko, YA, Yu, PY, Yang, TJ, Chiang, PC, Hsu, ST, Lin, YL, Lee, CC, Wu, HC & Tao, MH 2022, 'A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants', Journal of Biomedical Science, vol. 29, no. 1, 49. https://doi.org/10.1186/s12929-022-00830-1

TY - JOUR

T1 - A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

AU - Lee, I. Jung

AU - Sun, Cheng Pu

AU - Wu, Ping Yi

AU - Lan, Yu Hua

AU - Wang, I. Hsuan

AU - Liu, Wen Chun

AU - Yuan, Joyce Pei Yi

AU - Chang, Yu Wei

AU - Tseng, Sheng Che

AU - Tsung, Szu I.

AU - Chou, Yu Chi

AU - Kumari, Monika

AU - Lin, Yin Shiou

AU - Chen, Hui Feng

AU - Chen, Tsung Yen

AU - Lin, Chih Chao

AU - Chiu, Chi Wen

AU - Hsieh, Chung Hsuan

AU - Chuang, Cheng Ying

AU - Cheng, Chao Min

AU - Lin, Hsiu Ting

AU - Chen, Wan Yu

AU - Hsu, Fu Fei

AU - Hong, Ming Hsiang

AU - Liao, Chun Che

AU - Chang, Chih Shin

AU - Liang, Jian Jong

AU - Ma, Hsiu Hua

AU - Chiang, Ming Tsai

AU - Liao, Hsin Ni

AU - Ko, Hui Ying

AU - Chen, Liang Yu

AU - Ko, Yi An

AU - Yu, Pei Yu

AU - Yang, Tzu Jing

AU - Chiang, Po Cheng

AU - Hsu, Shang Te

AU - Lin, Yi Ling

AU - Lee, Chong Chou

AU - Wu, Han Chung

AU - Tao, Mi Hua

PY - 2022/12

Y1 - 2022/12

N2 - Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods: We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

AB - Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods: We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

KW - Booster dose

KW - COVID-19

KW - Cross-protectivity

KW - Hybrid vaccine

KW - Next generation vaccine

KW - Omicron vaccine

KW - SARS-CoV-2

KW - Variants of concern

KW - mRNA vaccine

UR - https://www.scopus.com/pages/publications/85133550386

U2 - 10.1186/s12929-022-00830-1

DO - 10.1186/s12929-022-00830-1

M3 - Article

C2 - 35799178

AN - SCOPUS:85133550386

SN - 1021-7770

VL - 29

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

IS - 1

M1 - 49

ER -

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

Abstract

Keywords

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