Safety and immunogenicity of a recombinant interferon-armed RBD dimer vaccine (V-01) for COVID-19 in healthy adults: a randomized, double-blind, placebo-controlled, Phase I trial

Abstract

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in preclinical study, which supported progression to Phase Ⅰ clinical trials in humans.A Randomized, double-blind, placebo-controlled phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February, 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive vaccine (10, 25, and 50μg) or placebo (V-01: Placebo=4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed promising safety profile with approximately 25% vaccine related overall adverse events within 30 days and no grade 3 or worse adverse events. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10μg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in phase Ⅱ/Ⅲ clinical trials.

Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen

“…In our study, the safety and reactogenicity profile following a homogenous booster dose exhibited an encouraging local/systemic safety and reactogenicity profile within 7 days post the homogenous booster immunization of V-01, when compared to the safety results from phase Ⅰ trial in same cohorts after receiving each dose of 10µg V-01 25 . Our findings are consistent with other studies using a homogenous prime-boost strategy.…”

“…We initiated a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Eligible participants were those who completed the initial two-dose regimens of 10μg V-01 in phase I trial 25 4-5 months earlier and who did not meet the withdrawal criteria, voluntarily consented to participate in this trial, agreed to take effective contraceptive measures (women of childbearing potential) during the study, and without a history of SARS-CoV-2 infection or close contact to asymptomatic individuals. Exclusion criteria were: receipt of a COVID-19 vaccine other than V-01; hyperpyrexia (axillary temperature ≥ 39.0°C) lasting ≥3 days following a previous V-01 administration; severe or medically attended allergic reactions following a previous V-01 inoculation; newly diagnosed severe chronic diseases or pre-existing chronic diseases poorly controlled by medication following primary V-01 immunization (for participants ≥60 years of age); any confirmed or suspected immunosuppression or immunodeficiency state as determined by medical history (e.g.…”

Broad neutralization against SARS-CoV-2 variants induced by a next-generation protein vaccine V-01

“…In the clinical trials, participants receiving V-01 presented 3- to 4-fold higher serum neutralizing antibody (nAb) titers to the original SARS-CoV-2 strain than convalescent sera. V-01 also demonstrated an excellent safety profile in both younger and even elder groups in phase I and phase II trials 3 , 4 , respectively.…”

Amantadine-assembled nanostimulator enhances dimeric RBD antigen-elicited cross-neutralization against SARS-CoV-2 strains

“…However, monomeric RBD requires a high vaccination dosage and only induces modest immune response without potent immunostimulatorys in the human body [22] . In comparison to monomeric RBD, dimeric RBD have stronger anti-degradation ability, more stable epitope conformation and more sufficient immunogenicity [22] , [24] . We therefore selected dimeric RBD as the antigen in this study.…”

“…For the design of antigen, receptor-binding domain (RBD) derived from spike protein has been widely used as the antigen of anti-SARS-CoV-2 vaccines and can elicit satisfactory neutralizing antibody response in vivo, which is 1.9～4.6-fold stronger than that in COVID-19 convalescent patients [17] , [18] , [19] , [20] . In comparison to monomeric RBD, dimeric RBD possesses more stable epitope conformation and anti-biodegradation capability in vivo [21] , both of which are important for inducing the high-level neutralizing antibody response [22] , [23] , [24] . For the selection of immunostimulator, amantadine as a well-known medication has a good biocompatibility and has been approved by FDA in large-scale clinical applications.…”