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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 2022More...
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
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