Kashiwagi Yasuyo, Maeda Mika, Kawashima Hisashi, Nakayama Tetsuo
Department of Pediatrics, Tokyo Medical University, Tokyo 160-0023, Japan.
Kitasato Institute for Life Sciences, Laboratory of Viral Infection, Tokyo 108-8641, Japan.
Vaccine. 2014 Jun 5;32(27):3393-401. doi: 10.1016/j.vaccine.2014.04.018. Epub 2014 Apr 24.
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 48h, 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-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine 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.
在美国和欧盟，铝佐剂疫苗通过肌肉注射（IM）给药，然而，在日本建议皮下注射（SC），因为此前有报道称多次肌肉注射抗生素后会出现严重的肌肉挛缩。新引入的佐剂疫苗，如人乳头瘤病毒（HPV）疫苗，建议通过肌肉注射。在本研究中，对目前可用的疫苗在小鼠中进行了肌肉注射评估。铝佐剂疫苗在注射部位诱导炎性结节，这些结节扩展到肌肉间隙，没有任何肌肉变性或坏死，而非佐剂疫苗则不会。这些结节在最初48小时内由多形核中性粒细胞和一些嗜酸性粒细胞组成，1个月后则由单核细胞/巨噬细胞组成。肌肉注射6个月后观察到炎性结节，其大小减小，肌肉注射12个月后被吸收，这比皮下注射后更早。在注射的肌肉组织中检测细胞因子产生情况，AS04佐剂HPV在肌肉组织中诱导的IL-1β、IL-6、KC、MIP-1和G-CSF水平高于任何其他疫苗，但观察到的血清细胞因子谱与其他疫苗诱导产生的相似。目前可用的疫苗不会像过去多次肌肉注射抗生素导致肌肉挛缩那样引起肌肉变性或纤维化瘢痕。
