Immunological Analysis of Nodavirus Capsid Displaying the Domain III of Japanese Encephalitis Virus Envelope Protein.

Kiven Kumar,Wen Siang Tan,Siti Suri Arshad,Kok Lian Ho,Hui Kian Ong

doi:10.3390/pharmaceutics13111826

Kiven Kumar, Wen Siang Tan + Show 3 more

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https://doi.org/10.3390/pharmaceutics13111826

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Journal: Pharmaceutics	Publication Date: Nov 1, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Universiti Putra Malaysia

Abstract

Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20–30%, of which, 30–50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current therapeutic approaches against JEV, vaccination remains the only effective approach to prevent the viral infection. Currently, live-attenuated and chimeric-live vaccines are widely used worldwide but these vaccines pose a risk of virulence restoration. Therefore, continuing development of JE vaccines with higher safety profiles and better protective efficacies is urgently needed. In this study, the Macrobrachium rosenbergii nodavirus (MrNV) capsid protein (CP) fused with the domain III of JEV envelope protein (JEV-DIII) was produced in Escherichia coli. The fusion protein (MrNV-CPJEV-DIII) assembled into virus-like particles (VLPs) with a diameter of approximately 18 nm. The BALB/c mice injected with the VLPs alone or in the presence of alum successfully elicited the production of anti-JEV-DIII antibody, with titers significantly higher than that in mice immunized with IMOJEV, a commercially available vaccine. Immunophenotyping showed that the MrNV-CPJEV-DIII supplemented with alum triggered proliferation of cytotoxic T-lymphocytes, macrophages, and natural killer (NK) cells. Additionally, cytokine profiles of the immunized mice revealed activities of cytotoxic T-lymphocytes, macrophages, and NK cells, indicating the activation of adaptive cellular and innate immune responses mediated by MrNV-CPJEV-DIII VLPs. Induction of innate, humoral, and cellular immune responses by the MrNV-CPJEV-DIII VLPs suggest that the chimeric protein is a promising JEV vaccine candidate.

Highlights

The Japanese encephalitis virus (JEV) is a vector-borne zoonotic virus responsible for encephalitis in domestic animals, including humans
The immunophenotyping results of this study demonstrated that the BALB/c mice immunized with Macrobrachium rosenbergii nodavirus (MrNV)-CPJEV-DIII with or without alum showed significant higher ratios of CD8+ /CD4+ (CTL to T lymphocytes (Th)) as compared to that of IMOJEV, but insignificant if compared to that of MrNV-capsid protein (CP)
We have demonstrated that the MrNV-CPJEV-DIII virus-like particles (VLPs) expressed in

Summary

Introduction

The Japanese encephalitis virus (JEV) is a vector-borne zoonotic virus responsible for encephalitis in domestic animals, including humans. JEV is detected in most of Asian and Oceania countries, including China, Japan, Taiwan, South Korea, Vietnam, Thailand, India, Sri Lanka, Cambodia, Indonesia, Philippines, Australia, and Malaysia [1,2]. JEV was detected in African and European countries [3,4,5]. Aquatic wading birds have been identified as reservoirs, while pigs and bats represent the virus-amplifying hosts, whereas the dead-end hosts comprise humans and equid. Humans can be infected by JEV via bites of the mosquito, Culex tritaeniorhynchus. Japanese encephalitis (JE) patients develop early mild symptoms such as fever, diarrhea, rigor, and headache, followed by more severe symptoms, including sudden onset of headache, neck stiffness, disorientation, Pharmaceutics 2021, 13, 1826.

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