The safety, immunogenicity, and efficacy of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: a randomized, open-label, active-controlled phase 3 trial

ABSTRACT

Continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enhanced transmissibility, significant immune escape, and waning immunity call for booster vaccination. We evaluated the safety, immunogenicity, and efficacy of heterologous booster with a SARS-CoV-2 mRNA vaccine SYS6006 versus an active control vaccine in a randomized, open-label, active-controlled phase 3 trial in healthy adults aged 18 years or more who had received two or three doses of SARS-CoV-2 inactivated vaccine in China. The trial started in December 2022 and lasted for 6 months. The participants were randomized (overall ratio: 3:1) to receive one dose of SYS6006 (N = 2999) or an ancestral receptor binding region-based, alum-adjuvanted recombinant protein SARS-CoV-2 vaccine (N = 1000), including 520 participants in an immunogenicity subgroup. SYS6006 boosting showed good safety profiles with most AEs being grade 1 or 2, and induced robust wild-type and Omicron BA.5 neutralizing antibody response on Days 14 and 28, demonstrating immunogenicity superiority versus the control vaccine and meeting the primary objective. The relative vaccine efficacy against COVID-19 of any severity was 51.6% (95% CI, 35.5–63.7) for any variant, 66.8% (48.6–78.5) for BA.5, and 37.7% (2.4–60.3) for XBB, from Day 7 through Month 6. In the vaccinated and infected hybrid immune participants, the relative vaccine efficacy was 68.4% (31.1–85.5) against COVID-19 of any severity caused by a second infection. All COVID-19 cases were mild. SYS6006 heterologous boosting demonstrated good safety, superior immunogenicity and high efficacy against BA.5-associated COVID-19, and protected against XBB-associated COVID-19, particularly in the hybrid immune population.

Trial registration: Chinese Clinical Trial Registry: ChiCTR2200066941

KEYWORDS:

• SARS-CoV-2
• mRNA vaccine
• heterologous boosting
• safety
• immunogenicity
• efficacy

Acknowledgements

We thank all the participants in the trial and our external service providers (contract research organizations, laboratories, clinical suppliers, and biostatistics providers) for their assistance.

Disclosure statement

Li CL, Yang HY, Qiu YZ, Zhong X, Ji QL, Zhou FF, Liu KL, Ji L, Wu SQ are the full-time employees of CSPC Megalith Biopharmaceutical Co., Ltd. Li CL and Yang HY are stock owners. All other authors declare no competing interest.

Additional information

Funding

This work was supported by CSPC Megalith Biopharmaceutical Co. Ltd.