Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: a phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults.
Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: a phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults.
复制标题
DOI：
10.3390/v4113227
复制
发表时间：
2012-11-19
期刊：
影响因子：
--
通讯作者：
Yusibov V
中科院分区：
文献类型：
--
作者：
Chichester JA;Jones RM;Green BJ;Stow M;Miao F;Moonsammy G;Streatfield SJ;Yusibov V
最近，我们报道了一种基于a/ Indonesia/05/2005 （H5N1）流感病毒株重组血凝素蛋白的亚单位流感候选疫苗，利用基于“发射载体”的短暂表达技术在烟叶中生产，并在临床前研究中证明了其免疫原性。在这里，我们展示了一项首次在人体中进行的随机、双盲、安慰剂对照研究的结果，该研究旨在研究该疫苗的三个递增剂量水平，即HAI-05、（15、45和90µg）加Alhydrogel®（每剂量0.75 mg铝）和不加Alhydrogel®的90µg剂量水平的安全性、反应原性和免疫原性。对18-49岁的健康成年人进行两次肌肉注射，间隔三周。在所有剂量水平下，疫苗总体上是安全且耐受性良好的，未报告严重不良事件或剂量限制性毒性。在所有疫苗剂量组和安慰剂组均观察到轻微的局部和全身反应，其发生与剂量无关。接种Alhydrogel®疫苗组的发病率更高。在血凝抑制和病毒微中和抗体滴度方面，HAI-05疫苗引起的免疫应答是可变的，在90µg无佐剂组观察到最高的应答。
Recently, we have reported on a subunit influenza vaccine candidate based on the recombinant hemagglutinin protein from the A/Indonesia/05/2005 (H5N1) strain of influenza virus, produced it using ‘launch vector’-based transient expression technology in Nicotiana benthamiana, and demonstrated its immunogenicity in pre-clinical studies. Here, we present the results of a first-in-human, Phase 1 randomized, double-blind, placebo-controlled study designed to investigate safety, reactogenicity and immunogenicity of three escalating dose levels of this vaccine, HAI-05, (15, 45 and 90 µg) adjuvanted with Alhydrogel® (0.75 mg aluminum per dose) and the 90 µg dose level without Alhydrogel®. Vaccine was administered intramuscularly in two injections three weeks apart to healthy adults of 18–49 years of age. At all dose levels the vaccine was generally safe and well tolerated, with no reported serious adverse events or dose-limiting toxicities. Mild local and systemic reactions were observed in all vaccine dose groups and the placebo group and their occurrence was not dose related. The incidence rates were higher in the groups receiving vaccine with Alhydrogel®. The immune response elicited by the HAI-05 vaccine was variable with respect to both hemagglutination-inhibition and virus microneutralization antibody titers, with the highest responses observed in the 90 µg unadjuvanted group.
登录
查看更多内容
影响因子：
4.4
作者：
Gillard, Paul;Caplanusi, Adrian;Schwarz, Tino F.
通讯作者：
Schwarz, Tino F.
影响因子：
6.4
作者：
Keitel, Wendy A.;Campbell, James D.;Hill, Heather
通讯作者：
Hill, Heather
影响因子：
168.9
作者：
Liang, Xiao-Feng;Wang, Hua-Qing;Wang, Yu
通讯作者：
Wang, Yu
影响因子：
158.5
作者：
Ehrlich, Hartmut J.;Mueller, Markus;Barrett, P. Noel
通讯作者：
Barrett, P. Noel
影响因子：
5.4
作者：
Khurana, Surender;Wu, Jian;Golding, Hana
通讯作者：
Golding, Hana