Sequential intramuscular immunization with chimeric hemagglutinins (cHA) composed of the same conserved HA stalk domain and distinct HA heads is a proposed strategy to produce a supra-seasonal universal influenza vaccine. To evaluate the local tolerance and the local and systemic effects of this strategy, two studies were performed in rabbits. In the first study, two different split virion monovalent cHA vaccines, containing cH5/1N1 and cH8/1N1, with or without AS01 or AS03, were injected at a two-week interval. In the second study, animals were given these vaccines and two weeks later an additional dose of split virion monovalent cHA vaccine containing cH11/1N1, with or without AS01 or AS03. General health status, rectal temperature, local tolerance, ophthalmology, hematology, coagulation, and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed three days after the last dose and after a treatment-free recovery period. The treatment-related changes included body weight loss and food consumption decrease, increases in neutrophil count, C-reactive protein and fibrinogen levels. Microscopic signs of inflammation at the injection sites and immune stimulation of the draining lymph nodes and spleen were also noticed. Most post-injection findings could be linked to the transient inflammation due to the establishment of the desired vaccine-elicited immune response, and were mainly observed in the adjuvanted groups. In conclusion, the sequential administration of different cHA vaccines was locally and systemically well-tolerated in rabbits.

中文翻译：

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通过肌内途径顺序施用的嵌合血凝素超季节季节性通用流感疫苗候选物在兔子中是局部和全身良好耐受的。

用嵌合的血凝素（cHA）（由相同的保守HA茎结构域和不同的HA头部组成）进行的顺序肌内免疫是生产季节性超常规流感疫苗的一种提议策略。为了评估该策略的局部耐受性以及局部和全身作用，在兔中进行了两项研究。在第一项研究中，每两周间隔注射两种不同的分开的病毒粒子单价cHA疫苗，其中包含cH5 / 1N1和cH8 / 1N1，带有或不带有AS01或AS03。在第二项研究中，给动物接种了这些疫苗，两周后又添加了一剂含cH11 / 1N1的分裂病毒粒子单价cHA疫苗，有或没有AS01或AS03。监测总体健康状况，直肠温度，局部耐受性，眼科，血液学，凝血和血液化学参数。在最后一次给药后三天和无治疗的恢复期后进行宏观和微观评估。与治疗有关的变化包括体重减轻和食物消耗减少，中性粒细胞计数，C反应蛋白和纤维蛋白原水平的增加。还观察到注射部位炎症的微观征兆以及引流淋巴结和脾脏的免疫刺激。由于建立了所需的疫苗引发的免疫反应，大多数注射后的发现可能与短暂的炎症有关，并且主要在佐剂组中观察到。总之，在兔子中，局部和系统耐受性良好，不同cHA疫苗的顺序给药是局部的。