Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study.
Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study.
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DOI：
10.1016/j.vaccine.2014.09.034
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发表时间：
2014-11-12
期刊：
影响因子：
5.5
通讯作者：
Petrovsky N
中科院分区：
文献类型：
--
作者：
Gordon D;Kelley P;Heinzel S;Cooper P;Petrovsky N
需要额外的安全和有效的人疫苗佐剂。Advax是一种新型佐剂，由δ菊粉的半结晶颗粒制成。在动物研究中，Advax增强了对乙型肝炎B表面抗原（HBsAg）的体液和细胞免疫，而不诱导局部或全身反应原性。这项首次人体I期临床试验在一组健康成人受试者中测试了三种肌内注射剂量的HBsAg（与Advax一起配制）的安全性和耐受性。Advax耐受性良好，注射部位疼痛评分与接受HBsAg单药治疗的受试者无显著差异，接受Advax治疗的受试者未报告不良事件。三次免疫后，Advax 5 mg组的血清保护力和抗HLA-Ab几何平均滴度（GMT）较高，（血清保护5/6，83.3%，GMT 40.7，95% CI 11.9-139.1）和10 mg（血清保护4/5，80%，GMT 51.6，95% CI 10.0-266.2）组与单独HBsAg（血清保护1/5，20%，GMT 4.1，95% CI 1.3-12.8）。同样，Advax 5 mg组（4/6，67%）和Advax 10 mg组（4/5，80%）中HBsAg阳性CD 4 T细胞应答的受试者比例高于HBsAg单药治疗组（1/5，20%）。这些结果证实了在临床前研究中观察到的Advax佐剂的安全性、耐受性和免疫原性。Advax可能是预防性人类疫苗中明矾佐剂的合适替代品，但需在更大规模研究中确认当前结果。澳大利亚和新西兰临床试验注册中心：ACTRN 12607000598482
There is a need for additional safe and effective human vaccine adjuvants. Advax is a novel adjuvant produced from semi-crystalline particles of delta inulin. In animal studies Advax enhanced humoral and cellular immunity to hepatitis B surface antigen (HBsAg) without inducing local or systemic reactogenicity. This first-in-man Phase 1 clinical trial tested the safety and tolerability of three intramuscular doses of HBsAg formulated with Advax in a group of healthy adult subjects. Advax was well tolerated with injection site pain scores not significantly different to subjects receiving HBsAg alone and no adverse events were reported in subjects that received Advax. Seroprotection and HBsAb geometric mean titers (GMT) after three immunizations were higher in the Advax 5mg (seroprotection 5/6, 83.3%, GMT 40.7, 95% CI 11.9–139.1) and 10mg (seroprotection 4/5, 80%, GMT 51.6, 95% CI 10.0–266.2) groups versus HBsAg alone (seroprotection 1/5, 20%, GMT 4.1, 95% CI 1.3–12.8). Similarly the proportion of subjects with positive CD4 T-cell responses to HBsAg was higher in the Advax 5mg (4/6, 67%) and Advax 10mg (4/5, 80%) groups versus HBsAg alone (1/5, 20%). These results confirm the safety, tolerability and immunogenicity of Advax adjuvant observed in preclinical studies. Advax may represent a suitable replacement for alum adjuvants in prophylactic human vaccines subject to confirmation of current results in larger studies. Australia and New Zealand Clinical Trial Registry: ACTRN12607000598482
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影响因子：
5.5
作者：
Gordon DL;Sajkov D;Woodman RJ;Honda-Okubo Y;Cox MM;Heinzel S;Petrovsky N
通讯作者：
Petrovsky N
影响因子：
6.2
作者：
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通讯作者：
Mackie, David
影响因子：
4.3
作者：
Cooper, Peter D.;Petrovsky, Nikolai
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影响因子：
9.1
作者：
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通讯作者：
Heathcote, J
影响因子：
5.5
作者：
Honda-Okubo Y;Saade F;Petrovsky N
通讯作者：
Petrovsky N