含有单磷酰脂质A和QS-21的疫苗佐剂系统可诱导针对乙肝表面抗原的强烈体液免疫和细胞免疫反应，且在接种疫苗后至少持续4年。
Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination.
作者信息
Leroux-Roels Geert, Van Belle Pascale, Vandepapeliere Pierre, Horsmans Yves, Janssens Michel, Carletti Isabelle, Garçon Nathalie, Wettendorff Martine, Van Mechelen Marcelle
机构信息
Centre for Vaccinology, Ghent University and Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
GlaxoSmithKline Vaccines, Rue de l'Institut 89, 1345 Rixensart, Belgium.
出版信息
Vaccine. 2015 Feb 18;33(8):1084-91. doi: 10.1016/j.vaccine.2014.10.078. Epub 2014 Nov 7.
BACKGROUND
Recombinant hepatitis B surface antigen (HBsAg) was used as a model antigen to evaluate persistence of cellular and humoral immune responses when formulated with three different Adjuvant Systems containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS-21, in an oil-in-water emulsion (AS02B and AS02V), or with liposomes (AS01B).
METHODS
This is an open, 4-year follow-up of a previous randomised, double-blind study. Healthy subjects aged 18-40 years received three vaccine doses on a month 0, 1, 10 schedule and were initially followed for 18 months. A total of 93 subjects (AS02B: n=30; AS02V: n=28; AS01B: n=35) were enrolled in this follow-up and had an additional blood sample taken at Year 4 (NCT02153320). The primary endpoint was the frequency of HBsAg-specific CD4(+) and CD8(+) T-cells expressing cytokines upon short-term in vitro stimulation of peripheral blood mononuclear cells with HBsAg-derived peptides. Secondary endpoints were anti-HBs antibody titres and frequency of HBsAg-specific memory B-cells.
RESULTS
A strong and persistent specific CD4(+) T-cell response was observed at Year 4 in all groups. HBsAg-specific CD4(+) T-cells expressed mainly CD40L and IL-2, and to a lesser extent TNF-α and IFN-γ. HBsAg-specific CD8(+) T-cells were not detected in any group. A high, persistent HBsAg-specific humoral immune response was observed in all groups, with all subjects seroprotected (antibody titre ≥10mIU/mL) at Year 4. The geometric mean antibody titre at Year 4 was above 100,000mIU/mL in all groups. A strong memory B-cell response was observed post-dose 2, which tended to increase post-dose 3 and persisted at Year 4 in all groups.
CONCLUSION
The MPL/QS-21/HBsAg vaccine formulations induced persistent immune responses up to 4 years after first vaccination. These Adjuvant Systems offer potential for combination with recombinant, synthetic or highly purified subunit vaccines, particularly for vaccination against challenging diseases, or in specific populations, although additional studies are needed.
背景
重组乙型肝炎表面抗原（HBsAg）被用作模型抗原，以评估其与三种不同佐剂系统（含3-O-去酰基-4'-单磷酸脂A（MPL）和QS-21）联合使用时细胞免疫和体液免疫反应的持久性。这三种佐剂系统分别为水包油乳剂（AS02B和AS02V）或脂质体（AS01B）。
方法
这是一项对先前随机双盲研究的开放、4年随访。18至40岁的健康受试者按0、1、10月的日程接种三剂疫苗，最初随访18个月。共有93名受试者（AS02B组：n = 30；AS02V组：n = 28；AS01B组：n = 35）纳入本次随访，并在第4年采集额外的血样（NCT02153320）。主要终点是用HBsAg衍生肽对外周血单核细胞进行短期体外刺激后，表达细胞因子的HBsAg特异性CD4(+)和CD8(+) T细胞的频率。次要终点是抗-HBs抗体滴度和HBsAg特异性记忆B细胞的频率。
结果
在第4年时，所有组均观察到强烈且持久的特异性CD4(+) T细胞反应。HBsAg特异性CD4(+) T细胞主要表达CD40L和IL-2，其次是TNF-α和IFN-γ。所有组均未检测到HBsAg特异性CD8(+) T细胞。所有组均观察到高且持久的HBsAg特异性体液免疫反应，在第4年时所有受试者均获得血清保护（抗体滴度≥10mIU/mL）。所有组在第4年时的几何平均抗体滴度均高于100,000mIU/mL。在第2剂疫苗接种后观察到强烈的记忆B细胞反应，在第3剂疫苗接种后趋于增加，并在第4年时在所有组中持续存在。
结论
MPL/QS-21/HBsAg疫苗制剂在首次接种后4年内诱导出持久的免疫反应。这些佐剂系统具有与重组、合成或高度纯化的亚单位疫苗联合使用的潜力，特别是用于针对具有挑战性的疾病的疫苗接种或特定人群，但仍需进一步研究。
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