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; clinical trial; fusion protein; heterologous boosting; subunit vaccine.

Conflict of interest 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.

Figures

Figure 1.

Summary of participants. The primary efficacy analysis was performed based on the modified intent-to-treat (mITT) set. A total of 10,241 eligible participants were randomly assigned to receive V-01 vaccine or placebo. After a 2-month follow-up, 4,935 participants in the V-01 vaccine group and 4,934 in the placebo group were included in the MITT. Of these, 199 and 221 participants in V-01 vaccine and placebo group, respectively, formed the immunogenicity analysis set, blood samples were obtained at baseline and at days 14 and 28 to assess the anti-SARS-CoV-2 neutralizing antibody titres.

Figure 2.

Efficacy of heterologous boost with V-01 vaccine preventing COVID-19 in subgroup according to mITT analysis. Vaccine efficacy was defined as the percentage reduction in the hazard ratio of V-01 vaccine group to the placebo group for the confirmed COVID-19. A stratified Cox proportional hazards model adjusting for covariates was applied to estimate the efficacy as well as its confidence interval.

Figure 3.

Virus-neutralizing titres pre- and post-booster. Serum was obtained before booster (day 0), 14, and 28 days after the booster vaccination. The neutralizing activity against ancestral strain was quantified by micro-dose cytopathogenic effect assays, with a limit of detection (LOD) of 10. The number above the scatter bars is the GMT for the group.

Figure 4.

Solicited Local and Systemic Adverse Events. Solicited local and systemic reactions were collected by diary cards within 7 days after booster from participants in the safety analysis set (5,108 and 5,110 participants in V-01 and placebo group, respectively). Solicited local reactions are shown in Panel A, and solicited systemic reactions are shown in Panel B. Each vertical bar represents the percentage of participants who reported the specified reaction with a 95% confidence interval.