ABSTRACT
Background: Reduced protection against COVID-19 due to the waning vaccine-induced immunity over time and emergence of immune-evading SARS-CoV-2 variants of concern (VOCs) indicate the need for vaccine boosters. LYB001 is an innovative recombinant SARS-CoV-2 vaccine which displays a repetitive array of the Spike glycoprotein's receptor binding domain (RBD) on a virus-like particle (VLP) vector to boost the immune system, produced using a Covalink plug-and-display protein binding technology. Methods: The safety and immunogenicity of LYB001 as a heterologous booster at an interval of 6-12 months was assessed in 119 participants receiving a booster with (1) 30g LYB001 (I-I-30L) or CoronaVac (I-I-C), (2) escalated dose of 60g LYB001 (I-I-60L) or CoronaVac in a ratio of 2:1 after two-dose primary series of inactivated COVID-19 vaccine in part 1 of this study, or (3) 30g LYB001 (I-I-I-30L) after three-dose primary series of inactivated COVID-19 vaccine in part 2 of this study. Results: A well-tolerated reactogenicity profile was observed for LYB001 as a heterologous booster, with adverse reactions predominantly being mild in severity and transient. The peak neutralizing antibody response was observed at 28 days after booster, with GMT (95%CI) against prototype SARS-CoV-2 being 1237.8 (747.2, 2050.6), 554.3 (374.6, 820.2), 181.9 (107.6, 307.6) and 1200.2 (831.5, 1732.3) in the I-I-30L, I-I-60L, I-I-C, and I-I-I-30L groups, respectively. LYB001 also elicited a cross-neutralizing antibody response against the BA.4/5 strain, dominant during the study period, with GMT being 201.1 (102.7, 393.7), 63.0 (35.1, 113.1), 29.2 (16.9, 50.3) and 115.3 (63.9, 208.1) at 28 days after booster in the I-I-30L, I-I-60L, I-I-C, and I-I-I-30L groups, respectively. Additionally, RBD-specific IFN-{gamma}, IL-2, IL-4 secreting T cells, as measured by ELISpot assay, dramatically increased (more than 10 times versus baseline) at 14 days after a single LYB001 booster. Conclusions: Our data confirm the favorable safety and immunogenicity profile of the LYB001 vaccine when used as a heterologous booster, and support the continued clinical development of this promising candidate that utilize VLP platform to provide protection against COVID-19.