目的:慢性HBV感染(CHB)的功能性治愈,而无需终身治疗,需要恢复HBV特异性体液和细胞免疫缺陷。基于主要结构和非结构蛋白的治疗性疫苗已在CHB患者中进行了测试,但已显示出稀缺的免疫原性。BRII-179,也称为VBI-2601,是由所有3个HBV表面包膜蛋白(前S1,前S2和S)组成的新型制剂。安全,抗病毒活性,在CHB患者中评估BRII-179与共佐剂干扰素(IFN)-α混合的免疫原性。
方法:这是随机的,开放标签,对照Ib/IIa期研究包括2个剂量水平,20μgBRII-179(部分1,n=25)和40μgBRII-179(部分2,n=24)。患者,在核苷(t)ide类似物(NA)治疗下受到病毒抑制的患者在第1部分中被随机分为3组:2:2,在第2部分中被随机分为2组:1:1,每月接受4次肌内注射BRII-179与/不与3MIUIFN-α混合。对HBsAg的抗体和细胞反应,以及循环HBsAg的演变进行监测。
结果:含/不含IFN-α的20μg和40μgBRII-179均耐受良好,无严重不良事件。BRII-179在所有治疗队列中>30%的患者中诱导抗-HBs反应,然而,仅在接受BRII-179和IFN-α的患者中观察到中度抗Pre-S1或抗Pre-S2抗体应答.BRII-179还恢复了S-,前S1-,在大多数治疗的患者中产生前S2特异性IFN-γ的T细胞。总的来说,BRII-179治疗后未观察到HBsAg显着降低。
结论:在NA治疗下的CHB患者中,BRII-179有/没有IFN-α表现出良好的安全性和诱导HBV特异性B和T细胞免疫反应。这些数据支持BRII-179与其他疗法组合的进一步临床评估。
背景:ACTRN12619001210167。
背景:BRII-179是一种治疗性疫苗,旨在改善慢性乙型肝炎患者的免疫反应。在这项研究中,BRII-179单独或与低剂量的干扰素-α是安全的,良好的耐受性,并诱导慢性乙型肝炎患者HBV特异性抗体和T细胞应答增强单独BRII-179治疗对患者的病毒学状态影响最小。BRII-179与其他药物联合实现功能性治愈的潜力正在临床中进行评估。
OBJECTIVE: Functional cure of chronic HBV infection (CHB) without life-long treatment requires the restoration of defective HBV-specific humoral and cellular immunity. Therapeutic vaccines based on the major structural and non-structural proteins have been tested in patients with CHB but have shown scarce immunogenicity. BRII-179, also known as VBI-2601, is a novel formulation comprised of all 3 HBV surface envelope proteins (Pre-S1, Pre-S2, and S). Safety, antiviral activity, and immunogenicity of BRII-179 admixed with co-adjuvant interferon (IFN)-α were assessed in patients with CHB.
METHODS: This randomized, open-label, controlled phase Ib/IIa study included 2 dose levels, 20 μg BRII-179 (Part 1, n = 25) and 40 μg BRII-179 (Part 2, n = 24). Patients, virally suppressed under nucleos(t)ide analogue (NA) therapy were randomized 1:2:2 into 3 cohorts in Part 1 and 1:1 into 2 cohorts in Part 2 to receive 4 monthly intramuscular injections of BRII-179 admixed with/without 3 MIU IFN-α. Antibody and cellular responses to HBsAg, as well as evolution of circulating HBsAg were monitored.
RESULTS: Both 20 μg and 40 μg BRII-179 with/without IFN-α were well tolerated with no severe adverse events. BRII-179 induced anti-HBs responses in >30% patients in all treatment cohorts, however, moderate anti-Pre-S1 or anti-Pre-S2 antibody responses were only observed in patients receiving BRII-179 with IFN-α. BRII-179 also restored S-, Pre-S1-, Pre-S2-specific IFN-γ-producing T-cells in the majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment.
CONCLUSIONS: In patients with CHB under NA therapy, BRII-179 with/without IFN-α exhibited a good safety profile and induced HBV-specific B- and T-cell immune responses. These data support further clinical evaluation of BRII-179 in combination with other therapies.
BACKGROUND: ACTRN12619001210167.
BACKGROUND: BRII-179 is a therapeutic vaccine designed to improve the immune response in patients with chronic hepatitis B. In this study, BRII-179 alone or with a low dose of interferon-α was safe, well tolerated, and induced enhanced HBV-specific antibody and T-cell responses in patients with chronic hepatitis B. However, BRII-179 treatment alone had minimal effect on patient\'s virological status. The potential of BRII-179 to achieve a functional cure in conjunction with other agents is being evaluated in the clinic.