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Open AccessArticle

Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines

by Chen Chen 1,2,3, Chengguang Zhang 1,2,3, Ruiming Li 1,2,3, Zongmei Wang 1,2,3, Yueming Yuan 1,2,3, Haoqi Li 1,2,3, Zhenfang Fu 1,2,3,4, Ming Zhou 1,2,3 and Ling Zhao 1,2,3,*
1
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan Hubei 430070, China
2
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan Hubei 430070, China
3
Key Laboratory of Preventive Veterinary Medicine of Hubei Province, Huazhong Agricultural University, Wuhan Hubei 430070, China
4
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(12), 1118; https://doi.org/10.3390/v11121118
Received: 12 November 2019 / Revised: 2 December 2019 / Accepted: 2 December 2019 / Published: 3 December 2019
(This article belongs to the Section Antivirals & Vaccines)
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.
Keywords: rabies virus; MPLA; inactivated vaccine; humoral immunity rabies virus; MPLA; inactivated vaccine; humoral immunity
MDPI and ACS Style

Chen, C.; Zhang, C.; Li, R.; Wang, Z.; Yuan, Y.; Li, H.; Fu, Z.; Zhou, M.; Zhao, L. Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines. Viruses 2019, 11, 1118.

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