Treanor John J, Chu Laurence, Essink Brandon, Muse Derek, El Sahly Hana M, Izikson Ruvim, Goldenthal Karen L, Patriarca Peter, Dunkle Lisa M
University of Rochester Medical Center, Rochester, NY, United States.
Benchmark Research, Austin, TX, United States.
Vaccine. 2017 Feb 7;35(6):923-928. doi: 10.1016/j.vaccine.2016.12.053. Epub 2017 Jan 11.
Influenza A viruses of the H5 subtype have been identified as important targets for development of vaccines. Achievement of potentially protective antibody responses against pandemic strains has usually required the use of adjuvants.
We evaluated a candidate A/Indonesia/05/2005 (H5) vaccine generated by baculovirus expression of recombinant hemagglutinin (HA) protein with or without stable emulsion (SE) as an adjuvant.
Healthy subjects 18-49years old were randomized (1:1:1:1) to receive two doses of rHA at 7.5ug per dose (no adjuvant), or 3.8ug, 7.5ug, or 15ug per dose formulated with 2% SE separated by 21days, and serum from day 0, 21, 42, and 201 assessed by hemagglutination-inhibition.
341 subjects were enrolled in the study and 321 received two doses of vaccine. Vaccination was well tolerated in all groups. After two doses, seroconversion was noted in only 9% (95% confidence interval 4%, 17%) of recipients of unadjuvanted vaccine at 7.5ug, but in 70% (59%, 80%), 76% (65%, 85%), and 83% (73%, 91%) of those receiving adjuvanted vaccine at 3.8ug, 7.5ug, or 15ug respectively.
Stable emulsion alone is an effective adjuvant for rH5 vaccine in healthy adults. All three adjuvanted dose groups met the current criterion for seroconversion rate for pandemic vaccines. This dose-ranging study also identified a group (15ug per dose formulated with 2% SE) that met the criteria for both seroconversion and percentage of subjects achieving an HI antibody titer⩾40. These Phase 2 data support the further clinical development of SE adjuvanted Panblok H5.
NCT01612000. The protocol was approved by the relevant Institutional Review Board for each study site, and the study was conducted in accordance with the Declaration of Helsinki, International Conference of Harmonisation - Good Clinical Practice, and all applicable laws and regulations. All participants provided written informed consent before study procedures.
H5亚型甲型流感病毒已被确定为疫苗研发的重要目标。针对大流行毒株产生潜在保护性抗体反应通常需要使用佐剂。
我们评估了一种候选A/印度尼西亚/05/2005（H5）疫苗，该疫苗通过杆状病毒表达重组血凝素（HA）蛋白制备，有或没有稳定乳液（SE）作为佐剂。
将18至49岁的健康受试者随机分为四组（1:1:1:1），分别接受两剂每剂7.5μg的重组HA疫苗（无佐剂），或每剂3.8μg、7.5μg或15μg且与2%SE配制的重组HA疫苗，间隔21天接种，在第0、21、42和201天采集血清，通过血凝抑制试验进行评估。
341名受试者参与了该研究，321人接受了两剂疫苗。所有组对疫苗接种的耐受性良好。两剂接种后，7.5μg无佐剂疫苗的接种者中只有9%（95%置信区间4%，17%）出现血清阳转，但在分别接受3.8μg、7.5μg或15μg佐剂疫苗的接种者中，血清阳转率分别为70%（59%，80%）、76%（65%，85%）和83%（73%，91%）。
单独的稳定乳液对健康成年人的重组H5疫苗是一种有效的佐剂。所有三个佐剂剂量组均符合当前大流行疫苗血清阳转率标准。这项剂量范围研究还确定了一组（每剂15μg与2%SE配制）既符合血清阳转标准又符合HI抗体效价≥40的受试者百分比标准。这些2期数据支持含SE佐剂的Panblok H5疫苗进一步开展临床研发。
NCT01612000。该方案已获得各研究地点相关机构审查委员会的批准，研究按照《赫尔辛基宣言》、国际协调会议 - 良好临床实践以及所有适用的法律法规进行。所有参与者在研究程序开始前均提供了书面知情同意书。
