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.
Subject(s)
COVID-19ABSTRACT
BACKGROUND: Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (ANM-SRP) is regarded as refractory myositis, whereby some patients respond poorly to conventional immunosuppression and require B cell depletion treatment. This study aimed to evaluate factors associated with refractory ANM-SRP. RESULTS: Clinical and pathological data from 48 patients with ANM-SRP were collected. We followed up clinical symptoms and image changes over 12 months. Univariate and multivariate analyses were undertaken to determine the associations between variables of interest and poor response to therapy. Refractory ANM-SRP appeared in 32.5% of patients who showed no or minimal improvement after 12 months of steroid therapy. The clinical risk factors for refractory patients were being male (OR, 19.57;P <0.001), severe muscle weakness (OR, 7.51;P <0.001) and concurrent interstitial lung disease (OR, 39.70;P <0.001). The imaging refractory-related factor was the fatty infiltration rate of thigh muscles over 3 months (P = 0.022) and the pathological factor associated with refractory ANM-SRP was the high expression of B cell activating factor receptor (BAFF-R) in muscle (P = 0.036). CONCLUSION: Being male, severe muscle weakness, concurrent interstitial lung disease, quick development of muscle fatty infiltration and more BAFF-R and B lymphocyte infiltration in muscle indicate a poor response to immunosuppressive therapy in patients with ANM-SRP.