Efficacy of heterologous boosting against SARS-CoV-2 using a recombinant interferon-armed fusion protein vaccine (V-01): a randomized, double-blind and placebo-controlled phase III trial

ABSTRACT

Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia. Each eligible participant received one dose of the V-01 vaccine developed by Livzon Mabpharm Inc. or placebo within the 3-6 months after the two-dose primary regimen, and was monitored for safety and efficacy. The primary endpoint was protection against confirmed symptomatic SARS-CoV-2 infection. A total of 10,218 participants were randomly assigned to receive a vaccine or placebo. Virus-neutralizing antibodies were assessed in 419 participants. A dramatic increase (11.3-fold; 128.3–1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6–64.7) according to the intention-to-treat principle. The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. Serious adverse events occurred almost equally in V-01 (0.12%) and placebo (0.16%) groups. The heterologous boosting with the V-01 vaccine was safe and efficacious, which could elicit robust humoral immunity under the epidemic of the Omicron variant.

Trial registration: ClinicalTrials.gov identifier: NCT05096832.

KEYWORDS:

• Efficacy
• heterologous boosting
• subunit vaccine
• clinical trial
• fusion protein

Acknowledgement

We thank DSMB members: Profs. Jie-Lai Xia, Xue-Dong Liu, Tie Xu, and Zheng Zhang for their invaluable contributions to this trial. We appreciate Drs. Zhi-Wei Jiang, and Li-Ping Lv (Beijing KeyTech Statistical Consulting Co., Ltd.) for their dedicated support in the statistical analysis and reporting of this study.

Disclosure statement

FJ, WD, and XY are employees of the Joincare Pharmaceutical Group Industry Co., Ltd.; ZHX, JMY, and YZ are employees of the Livzon Mabpharm Inc., Joincare holds Livzon. All other authors declare no competing interests.