NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing, China.
PLoS One. 2022 Jan 31;17(1):e0262231. doi: 10.1371/journal.pone.0262231. eCollection 2022.
The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-lasting protective antibodies and a cellular immune response in mice after three immunizations. Unfortunately, compared with the mice in RBF group, mice in RBF/Adju-Phos generated a serious Th2 humoral immune response that elicited Th2-mediated lung pathology. From the IL-4+:IFNγ+ ratio, there was also a robust Th2 cellullar immunologic response in the RBF/Adju-Phos group. This study demonstrates that it may not be enough for RBF to increase the titer of neutralizing antibodies. A balanced immune response must be induced for hRSV vaccine safety.
人类呼吸道合胞病毒（hRSV）疫苗的发展受到增强呼吸道疾病（ERD）风险的阻碍，这种风险是由高度偏向 Th2 免疫反应引起的。在我们之前的研究中，我们使用大肠杆菌 BL21 表达了重组前 F 蛋白，称为 RBF。为了验证 RBF 蛋白是否会引起 ERD，我们使用商业铝佐剂（GMP 级 Adju-Phos）测试了 RBF 的免疫原性和安全性。单独的 RBF 和 RBF/Adju-Phos 在三次免疫后可在小鼠中引起持久的保护性抗体和细胞免疫反应。不幸的是，与 RBF 组的小鼠相比，RBF/Adju-Phos 组的小鼠产生了严重的 Th2 体液免疫反应，引起了 Th2 介导的肺部病理学。从 IL-4+：IFNγ+ 比值来看，RBF/Adju-Phos 组也存在强烈的 Th2 细胞免疫反应。这项研究表明，增加中和抗体的滴度可能还不够。为了确保 hRSV 疫苗的安全性，必须诱导平衡的免疫反应。
