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Safety and Immunogenicity of Heterologous Boosting With a Protein-Subunit-Based COVID-19 Vaccine (ZF2001) in Healthy Adults Previously Received One Dose of Convidecia: A Randomised, Observer-Blinded, Placebo-Controlled Trial

36 Pages Posted: 10 Jan 2022

See all articles by Pengfei Jin

Pengfei Jin

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - NHC Key Laboratory of Enteric Pathogenic Microbiology

Xi-Ling Guo

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Wei Chen

Anhui Zhifei Longcom Biopharmaceutical Co. LTD.

Shihua Ma

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - Guanyun County Center for Disease Control and Prevention

Hong-Xing Pan

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Lianpan Dai

Chinese Academy of Sciences (CAS) - CAS Key Laboratory of Pathogenic Microbiology and Immunology

Pan Du

Nanjing Vazyme Biotech Co., Ltd.

Lili Wang

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - Guanyun County Center for Disease Control and Prevention

Lairun Jin

Southeast University

Yin Chen

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Feng-Juan Shi

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Jing-Xian Liu

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Xiao-Yu Xu

Nanjing Vazyme Biotech Co., Ltd.

Yanan Zhang

Anhui Zhifei Longcom Biopharmaceutical Co. LTD.

George F. Gao

Chinese Academy of Sciences (CAS) - CAS Key Laboratory of Pathogenic Microbiology and Immunology; University of Science and Technology of China (USTC) - School of Life Sciences

Cancan Chen

Anhui Zhifei Longcom Biopharmaceutical Co. LTD.

Jialu Feng

Nanjing Medical University

Jing-Xin Li

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Feng-Cai Zhu

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

More...

Abstract

Background: We assessed the safety and immunogenicity of heterologous schedules with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001).

Methods: We did a randomised, observer-blinded, placebo-controlled trial in healthy adults, vaccinated with a single dose of Convidecia 28 days before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either ZF001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day prime-boost intervals. For both regimens, all participants received the second immunisation with ZF2001 at 4 months after the first boost dose. Four permutations of prime-boost schedule were included: receiving Convidecia/ZF2001/ZF2001 at day 0, day 28 and month 5 ( referred to as C/Z/Z (D0-D28-M5)), C/Z (D0-M5), C/Z/Z (D0-D56-M6), and C/Z (D0-M6). Participants were masked to the vaccine received but not to the boosting interval. The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination.

Results: Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. A total of 26 participants (21·7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild . Among participants receiving ZF001 as second dose, the GMTs of neutralising antibodies increased to 58·4 IU/ml (42·8-79·8) in 0-28 regimen, and to 80·8 IU/ml (53·1-122·9) in 0-56 regimen at 14 days post first boost dose. While, the neutralizing antibodies of participants receiving TIV showed no increase. The GMTs of neutralising antibodies increased to 334·9 IU/ml (95% CI 230·4, 486·9) in C/Z/Z (D0-D28-M5) regimen, and 441·2 IU/ml (260·8, 746·4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. While, the GMTs of neutralising antibodies increased to 282·9 IU/ml (142·5, 561·8) in C/Z (D0-M5) regimen, and 293·9 IU/ml (137·6, 627·9) in C/Z (D0-M6), respectively.

Interpretation: ZF001 given as a boost dose in individuals primed with one dose of Convidecia is safe and highly efficient in eliciting humoral immunity. Funding The study was funded by National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Anhui Zhifei Longcom Biopharmaceutical Co., Ltd.

Trial Registration Details: This study is registered with NCT04833101.

Funding Information: The study was funded by National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Anhui Zhifei Longcom Biopharmaceutical Co., Ltd.

Declaration of Interests: WC, YZ and CC are the employees of Anhui Zhifei Longcom Biopharmaceutical. LD and GFG are listed in the patent as the inventors of the RBD dimer as a betacoronavirus vaccine. All other authors declare no competing interest.

Ethics Approval Statement: The trial protocol was reviewed and approved by the institutional review board of the Jiangsu Provincial Center of Disease Control and Prevention. All participants provided written 185 informed consent before enrollment.

Keywords: SARS-CoV-2, heterologous immunisation, recombinant adenovirus type-5-vectored COVID-19 vaccine, protein-subunit-based COVID-19 vaccine, clinical trial

Suggested Citation

Jin, Pengfei and Guo, Xi-Ling and Chen, Wei and Ma, Shihua and Pan, Hong-Xing and Dai, Lianpan and Du, Pan and Wang, Lili and Jin, Lairun and Chen, Yin and Shi, Feng-Juan and Liu, Jing-Xian and Xu, Xiao-Yu and Zhang, Yanan and Gao, George F. and Chen, Cancan and Feng, Jialu and Li, Jing-Xin and Zhu, Feng-Cai, Safety and Immunogenicity of Heterologous Boosting With a Protein-Subunit-Based COVID-19 Vaccine (ZF2001) in Healthy Adults Previously Received One Dose of Convidecia: A Randomised, Observer-Blinded, Placebo-Controlled Trial. Available at SSRN: https://ssrn.com/abstract=4005185 or http://dx.doi.org/10.2139/ssrn.4005185

Pengfei Jin

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Xi-Ling Guo

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Wei Chen

Anhui Zhifei Longcom Biopharmaceutical Co. LTD. ( email )

Hefei
China

Shihua Ma

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - Guanyun County Center for Disease Control and Prevention ( email )

Guanyun County
China

Hong-Xing Pan

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Lianpan Dai

Chinese Academy of Sciences (CAS) - CAS Key Laboratory of Pathogenic Microbiology and Immunology ( email )

52 Sanlihe Rd.
Datun Road, Anwai
Beijing, Xicheng District 100864
China

Pan Du

Nanjing Vazyme Biotech Co., Ltd. ( email )

Nanjing
China

Lili Wang

Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases - Guanyun County Center for Disease Control and Prevention ( email )

Guanyun County
China

Lairun Jin

Southeast University ( email )

Sipailou 2#
Nanjing, Jiangsu Province 210096
China

Yin Chen

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Feng-Juan Shi

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Jing-Xian Liu

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Xiao-Yu Xu

Nanjing Vazyme Biotech Co., Ltd. ( email )

Nanjing
China

Yanan Zhang

Anhui Zhifei Longcom Biopharmaceutical Co. LTD. ( email )

Hefei
China

George F. Gao

Chinese Academy of Sciences (CAS) - CAS Key Laboratory of Pathogenic Microbiology and Immunology ( email )

52 Sanlihe Rd.
Datun Road, Anwai
Beijing, Xicheng District 100864
China

University of Science and Technology of China (USTC) - School of Life Sciences ( email )

China

Cancan Chen

Anhui Zhifei Longcom Biopharmaceutical Co. LTD. ( email )

Hefei
China

Jialu Feng

Nanjing Medical University ( email )

300 Guangzhou Road
Nanjing, 210029
China

Jing-Xin Li

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Feng-Cai Zhu (Contact Author)

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

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