Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice

Xingxing Li; Jingjing Liu; Jingjing Liu; Wenjuan Li; Qinhua Peng; Miao Li; Zhifang Ying; Zelun Zhang; Xinyu Liu; Xiaohong Wu; Danhua Zhao; Lihong Yang; Shouchun Cao; Yanqiu Huang; Leitai Shi; Hongshan Xu; Yunpeng Wang; Guangzhi Yue; Yue Suo; Jianhui Nie; Weijin Huang; Jia Li; Yuhua Li

doi:10.3389/fimmu.2023.1142394

Frontiers in Immunology (Mar 2023)

Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice

Xingxing Li,
Jingjing Liu,
Jingjing Liu,
Wenjuan Li,
Qinhua Peng,
Miao Li,
Zhifang Ying,
Zelun Zhang,
Xinyu Liu,
Xiaohong Wu,
Danhua Zhao,
Lihong Yang,
Shouchun Cao,
Yanqiu Huang,
Leitai Shi,
Hongshan Xu,
Yunpeng Wang,
Guangzhi Yue,
Yue Suo,
Jianhui Nie,
Weijin Huang,
Jia Li,
Yuhua Li

Affiliations

Xingxing Li: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Jingjing Liu: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Jingjing Liu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Wenjuan Li: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Qinhua Peng: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Miao Li: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Zhifang Ying: Department of Respiratory Virus Vaccine, National Institutes for Food and Drug Control, Beijing, China
Zelun Zhang: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Xinyu Liu: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Xiaohong Wu: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Danhua Zhao: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Lihong Yang: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Shouchun Cao: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Yanqiu Huang: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Leitai Shi: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Hongshan Xu: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Yunpeng Wang: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Guangzhi Yue: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Yue Suo: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Jianhui Nie: Department of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
Weijin Huang: Department of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
Jia Li: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China
Yuhua Li: Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, China

DOI: https://doi.org/10.3389/fimmu.2023.1142394
Journal volume & issue: Vol. 14

Abstract

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The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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