The Eurocine® L3 adjuvants with subunit influenza antigens induce protective immunity in mice after intranasal vaccination
The Eurocine® L3 adjuvants with subunit influenza antigens induce protective immunity in mice after intranasal vaccination
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DOI：
10.1016/j.vaccine.2010.07.001
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发表时间：
2010-09-07
期刊：
影响因子：
5.5
通讯作者：
Lundkvist, Ake
中科院分区：
文献类型：
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作者：
Petersson, Pernilla;Hedenskog, Mona;Lundkvist, Ake
将鼻内 (i.n.) 施用流感亚单位抗原与脂质佐剂 (Eurocine (R)) 与皮下 (s.c.) 免疫的小鼠的免疫原性和保护功效进行比较。皮下接种组的流感血凝抑制 (HAI) 和 ELISA IgG 滴度相似。并在 i.n. 之后用佐剂进行疫苗接种。注射疫苗后，血清中病毒特异性 IgA 水平较高。与皮下免疫后相比，使用佐剂。仅在接种疫苗后（无论有或没有佐剂），才能在鼻洗液中测量病毒特异性 IgA。因此，i.n.与皮下注射相比，用内源性无毒脂质佐剂进行疫苗接种诱导了相同或更强的抗体反应。用相同的抗原进行免疫。我们进一步分析了小鼠模型中针对病毒攻击的保护功效。 A/New/Caledonia/20/99株的亚单位抗原制剂用于用不同佐剂组合对NMRI小鼠进行疫苗接种。小鼠在体内受到挑战。用6.5组织培养感染剂量(50)的同源病毒进行注射，3天后处死。由于该病毒对小鼠不致命，因此通过对尸检获得的肺组织进行定量实时 PCR 来测量其保护效果。仅用佐剂治疗的小鼠和首次接触小鼠组明显具有最高的平均病毒RNA拷贝数（分别为19.200和11.000）。所有接种疫苗的组的拷贝数均显着降低，尤其是注射 L3A 的小鼠。 （-中位数 120；i.n. L3B - 中位数 2.200；非佐剂皮下疫苗接种 - 中位数 2.600）。我们的发现促使进一步研究该制剂对雪貂、猴子和人类的影响。 (C) 2010 Elsevier Ltd. 保留所有权利。
The immunogenicity and protective efficacy in mice of intranasally (i.n.) administrated influenza subunit antigens together with lipid-based adjuvants (Eurocine (R)) were compared to those of subcutaneous (s.c.) immunisation. Influenza hemagglutination inhibition (HAI) and ELISA IgG titers were similar in the group's vaccinated s.c. and after i.n. vaccination with adjuvants. The virus-specific IgA levels in serum were higher after vaccination i.n. with adjuvant than after s.c immunisation. Virus-specific IgA was measurable in nasal washings only after i.n vaccinations, with and without adjuvants. Thus, i.n. vaccination with the endogenous non-toxic, lipid adjuvants induced equal or stronger antibody responses as compared to s.c. immunisation with the same antigen. We further analysed the protective efficacy against virus challenge in a mouse model. A subunit antigen preparation of the A/New/Caledonia/20/99 strain was used for vaccination of NMRI mice with different combinations of adjuvants. The mice were challenged i.n. with 6.5 tissue culture infectious doses(50) of homologous virus and sacrificed 3 days later. Since the virus is not lethal in mice, the protective efficacy was measured by quantitative, real-time PCR on pulmonary tissue, obtained at autopsy. The mice treated with only adjuvant and the group of nave mice clearly had the highest mean viral RNA copy numbers (19.200 and 11.000, respectively). All vaccinated groups had significantly lower copy numbers, especially the mice that received the L3A i.n. (-median 120; i.n. L3B - median 2.200; and non-adjuvanted s.c. vaccination - median 2.600). Our findings prompt further investigations of the effect of the formulations in ferrets, monkeys and man. (C) 2010 Elsevier Ltd. All rights reserved.