Yam Karen K, Gupta Jyotsana, Winter Kaitlin, Allen Elizabeth, Brewer Angela, Beaulieu Édith, Mallett Corey P, Burt David S, Ward Brian J
Department of Experimental Medicine, Research Institute of the McGill University Health Centre , Montreal, QC , Canada.
GSK Vaccines , Laval, QC , Canada.
Front Immunol. 2015 Apr 29;6:207. doi: 10.3389/fimmu.2015.00207. eCollection 2015.
During the 2009-2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted "high" (3 μg) and low-dose (0.03-0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted "high-dose" vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of "standard" doses of vaccines in pre-clinical vaccine studies.
在2009 - 2010年流感大流行期间，建议大多数加拿大人接种一种含佐剂、可减少剂量的疫苗。我们推测，对AS03佐剂低抗原（Ag）剂量疫苗与无佐剂全剂量疫苗的反应存在差异。我们研究了Ag剂量与水包油乳剂佐剂系统AS03之间的关系。BALB/c小鼠接受了两剂肌肉注射的AS03A或AS03B，同时使用了A/乌拉圭/716/2007 H3N2裂解病毒颗粒疫苗Ag的过度稀释液。在加强免疫3周后评估免疫反应。无佐剂的“高”（3μg）剂量和低剂量（0.03 - 0.003μg）疫苗在再次刺激的脾细胞中产生了相似的血清抗体滴度和细胞因子分泌模式。与无佐剂的“高剂量”疫苗接种相比，AS03A和AS03B佐剂的低剂量疫苗都倾向于引发更高的血清抗体滴度、更广泛的细胞因子分泌诱导，并在脾细胞中产生更多的流感特异性抗体分泌细胞以及细胞因子分泌的CD4和CD8 T细胞。我们表明，在这种流感疫苗接种小鼠模型中改变Ag和/或AS03剂量可强烈影响所引发免疫反应的强度和模式。鉴于含佐剂、可减少剂量疫苗扩大使用的可能性，这些发现具有高度相关性，并对临床前疫苗研究中“标准”剂量疫苗的使用提出了疑问。
