Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines

Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines
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DOI:
10.1016/j.vaccine.2014.04.018
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发表时间:
2014-06-05
期刊:
影响因子:
5.5
通讯作者:
Nakayama, Tetsuo
Nakayama, Tetsuo
中科院分区:
医学3区
文献类型:
--
作者:
Kashiwagi, Yasuyo;Maeda, Mika;Nakayama, Tetsuo

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在美国和欧盟,铝佐剂疫苗是通过肌肉注射(IM)接种的,但在日本,由于先前报道的多次肌肉注射抗生素后严重的肌肉痉挛,建议使用皮下注射(SC)。通过IM推荐了新引入的佐剂疫苗,如人乳头瘤病毒(HPV)疫苗。在目前的研究中,目前可用的疫苗是通过小鼠的IM进行评估的。铝佐剂疫苗在注射部位诱导炎性结节,这些炎性结节扩展到肌肉内间隙,没有任何肌肉退化或坏死,而非佐剂疫苗没有。这些结节在最初的48h内由多形的中性粒细胞和一些嗜酸性粒细胞组成,1个月后由单核/巨噬细胞组成。IM后6个月可见炎性结节,体积缩小,12个月后吸收,较SC后提前。在注射的肌肉组织中检测到细胞因子的产生,AS04佐剂HPV诱导的肌肉组织中IL-1β、IL-6、KC、MIP-1和G-CSF的水平高于其他疫苗,但血清细胞毒水平与其他疫苗相似。目前可用的疫苗不会像过去观察到的由多次注射抗生素引起的肌肉痉挛那样导致肌肉变性或纤维性瘢痕。(C)2014爱思唯尔有限公司。保留所有权利。
Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48 h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1 beta, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytoldne profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past. (C) 2014 Elsevier Ltd. All rights reserved.