Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines
Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines
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单磷酰脂质 A (MPLA) 是灭活狂犬病疫苗的有效佐剂
DOI：
10.3390/v11121118
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发表时间：
2019-12-01
期刊：
影响因子：
4.7
通讯作者：
Zhao, Ling
中科院分区：
文献类型：
--
作者：
Chen, Chen;Zhang, Chengguang;Zhao, Ling
狂犬病是世界上最具威胁性的人畜共患疾病之一，可引起致命的中枢神经系统疾病。到目前为止，接种狂犬病疫苗是预防和控制该病的最有效措施。目前，狂犬病灭活疫苗广泛用于人和家畜。然而，狂犬病灭活疫苗诱导的体液免疫应答相对较低，需要多次注射才能达到保护性免疫。添加佐剂是提高狂犬病灭活疫苗免疫原性的有效方法。在本研究中，我们发现，单磷酰脂质A（MPLA），一个众所周知的TLR 4激动剂，可以显着促进骨髓来源的树突状细胞（BMDC）的成熟，通过TLR 4依赖的途径在体外和在体内的常规DC（cDC）的成熟。MPLA作为狂犬病灭活疫苗的佐剂，能显著促进T滤泡辅助细胞（Tfh）、生殖中心B细胞和浆细胞（PC）的生成，从而提高狂犬病病毒特异性总IgG、IgG 2a、IgG 2 B和病毒中和抗体（VNA）的产生。MPLA还能提高RABV强毒攻击小鼠的存活率。总之，我们的结果表明，MPLA作为佐剂通过激活cDC-Tfh-GC B轴增强体液免疫应答的强度。我们的研究结果将有助于提高传统狂犬病疫苗的效率。
Rabies, as one of the most threatening zoonoses in the world, causes a fatal central nervous system (CNS) disease. So far, vaccination with rabies vaccines has been the most effective measure to prevent and control this disease. At present, inactivated rabies vaccines are widely used in humans and domestic animals. However, humoral immune responses induced by inactivated rabies vaccines are relatively low and multiple shots are required to achieve protective immunity. Supplementation with an adjuvant is a practical way to improve the immunogenicity of inactivated rabies vaccines. In this study, we found that monophosphoryl-lipid A (MPLA), a well-known TLR4 agonist, could significantly promote the maturation of bone marrow-derived dendritic cells (BMDC) through a TLR4-dependent pathway in vitro and the maturation of conventional DCs (cDCs) in vivo. We also found that MPLA, serving as an adjuvant for inactivated rabies vaccines, could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs), consequently enhancing the production of RABV-specific total-IgG, IgG2a, IgG2b, and the virus-neutralizing antibodies (VNAs). Furthermore, MPLA could increase the survival ratio of mice challenged with virulent RABV. In conclusion, our results demonstrate that MPLA serving as an adjuvant enhances the intensity of humoral immune responses by activating the cDC–Tfh–GC B axis. Our findings will contribute to the improvement of the efficiency of traditional rabies vaccines.