Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): a randomized, observer-blinded, placebo-controlled trial

Pengfei Jin,Pan Du,Yanan Zhang,Xiaoyu Xu,Fengcai Zhu,Xiling Guo,Cancan Chen,Jingxian Liu,Lairun Jin,Lianpan Dai,Lili Wang,Hongxing Pan,Jialu Feng,Fengjuan Shi,Shihua Ma,Wei Chen,George F Gao,Jingxin Li,Yin Chen

doi:10.1101/2022.02.24.22271445

Abstract

AbstractBackgroundHeterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001).Methods and FindingsWe did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). 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. 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. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV.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 neutralizing 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. The GMTs of neutralizing 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. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron.ConclusionsHeterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine.Trial RegistrationClinicalTrial.gov NCT04833101

Highlights

70 Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome71 coronavirus 2 (SARS-CoV-2), has severely impacted the world in terms of health, 72 society, and economy[1]
Between April 7, 2021, and May 6, 2021, a total of 120 adults over 18 years of age 262 who had received a primary dose of Convidecia were enrolled, among whom 60 were randomly assigned (2:1) to receive a dose of ZF2001 or a trivalent inactivated influenza vaccine (TIV) at an interval of 28
Our findings show that heterologous immunization of ZF001 in individuals whom were vaccinated with Convidecia is safe, showing the lower frequency of systemic adverse

Summary

Introduction

70 Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome71 coronavirus 2 (SARS-CoV-2), has severely impacted the world in terms of health, 72 society, and economy[1]. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. 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. Among participants receiving ZF001 as second dose, the GMTs of neutralizing 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. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. In the previous development of SARS and MERS vaccines, S protein was used as the most important candidate antigen

Methods

Results

Conclusion