Abstract：
Enterovirus D68 (EV-D68), a pathogen that causes respiratory symptoms, mainly in children, has been implicated in acute flaccid myelitis, which is a poliomyelitis-like paralysis. Currently, there are no licensed vaccines or treatments for EV-D68 infections. Here, we investigated the optimal viral inactivation reagents, vaccine adjuvants, and route of vaccination in mice to optimize an inactivated whole-virion (WV) vaccine against EV-D68. We used formalin, β-propiolactone (BPL), and hydrogen peroxide as viral inactivation reagents and compared their effects on antibody responses. Use of any of these three viral inactivation reagents effectively induced neutralizing antibodies. Moreover, the antibody response induced by the BPL-inactivated WV vaccine was enhanced when adjuvanted with cytosine phosphoguanine oligodeoxynucleotide (CpG ODN) or AddaVax (MF59-like adjuvant), but not with aluminum hydroxide (alum). Consistent with the antibody response results, the protective effect of the inactivated WV vaccine against the EV-D68 challenge was enhanced when adjuvanted with CpG ODN or AddaVax, but not with alum. Further, while the intranasal inactivated WV vaccine induced EV-D68-specific IgA antibodies in the respiratory tract, it was less protective against EV-D68 challenge than the injectable vaccine. Thus, an injectable inactivated EV-D68 WV vaccine prepared with appropriate viral inactivation reagents and an optimal adjuvant is a promising EV-D68 vaccine.
摘要：
肠道病毒D68(EV-D68),引起呼吸道症状的病原体，主要是儿童，与急性弛缓性脊髓炎有关,这是脊髓灰质炎样瘫痪。目前,没有针对EV-D68感染的许可疫苗或治疗方法.这里,我们研究了最佳的病毒灭活试剂，疫苗佐剂，和在小鼠中接种疫苗的途径以优化针对EV-D68的灭活全病毒体(WV)疫苗。我们用了福尔马林,β-丙内酯（BPL），和过氧化氢作为病毒灭活试剂，并比较了它们对抗体反应的影响。使用这三种病毒灭活试剂中的任一种有效地诱导中和抗体。此外，当用胞嘧啶磷酸鸟嘌呤寡脱氧核苷酸（CpGODN）或AddaVax（MF59样佐剂）佐剂时，BPL灭活的WV疫苗诱导的抗体应答增强，但不与氢氧化铝（明矾）。与抗体反应结果一致，当用CpGODN或AddaVax佐剂时，灭活疫苗对EV-D68攻击的保护作用增强，但不是明矾。Further,而鼻内灭活WV疫苗在呼吸道诱导EV-D68特异性IgA抗体，它对EV-D68攻击的保护作用低于注射疫苗.因此，用适当的病毒灭活试剂和最佳佐剂制备的可注射灭活EV-D68WV疫苗是一种有前途的EV-D68疫苗。
