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: .

Modelling the adjustment of COVID-19 response and exit from dynamic zero-COVID in China

“…Since more than 95% of vaccines administered in mainland China currently are inactivated virus vaccines, we assume that all vaccinees would receive inactivated virus vaccines (namely, BBIBP-CorV or CoronaVac) for the first three doses. The IC50 neutralising antibody (Ab) titres against Omicron after the first three doses were obtained from the Brazilian study RHH-001 6 and the Phase-3 trial of V-01 vaccine 20 .…”

“…RBD dimer-IFN-Pan Fc fusion protein) developed by Livzon. In the Phase-3 trial of 10,218 participants in Pakistan and Malaysia with a follow-up period of 60-90 days, the vaccine efficacy of V-01 as the third dose was 64% (23-83) and 39% (3-62) against Omicron infection among 4,935 participants who had received BBIBP-CorV or CoronaVac vaccines in their primary course 20 . 2) NVSI-06-08 is a recombinant COVID-19 vaccine based on the antigen of a mutation-integrated trimetric RBD developed by Sinopharm.…”

“…We apply the Khoury method to predict the vaccine effectiveness (VE) in reducing Omicron susceptibility and infectiousness as described in Leung et al 9 . The prediction is based on the neutralising Ab data from Brazil and Hong Kong 6,22,23 and the VE data from Phase-3 trial of V-01, RHH-01 study from Brazil, and UKHSA reports from the UK 6,20,24 . Using the same method, we model the waning of VE based on the following assumptions regarding the waning of Ab titres: (i)…”

A Heterologous V-01 or Variant-Matched Bivalent V-01D-351 Booster following Primary Series of Inactivated Vaccine Enhances the Neutralizing Capacity against SARS-CoV-2 Delta and Omicron Strains

“…Firstly, data should be interpreted with caution since the safety and immunogenicity profiles were concluded based on a relatively small sample size. The phase III booster study of V-01 with a larger sample size can provide further evidence regarding this matter [ 31 ]. In addition, analysis of cellular mediated immunity was not reported which was readily able to cross recognize VOCs [ 32 , 33 ] and provide protection from severe outcomes.…”

Recombinant Protein Vaccines against Human Betacoronaviruses: Strategies, Approaches and Progress

“…The results of phase 1 clinical trials have shown the vaccine’s immunogenicity, its ability to induce high titers of neutralizing antibodies and its safety and good tolerability [ 125 ]. The V-01 vaccine is currently undergoing phase 3 clinical trials and has been shown to induce sustained humoral immunity in study participants vaccinated with the inactivated vaccine (NCT05096832) [ 127 ]. It has been approved for use in China.…”