PH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine.

Weibin Zhang,Hong Zhang,Xiaodong Liu,Pingdong Lin,Anhua Xie,Fangnan Xiao,Chenyang Zheng,Fangman Chen,Chunhua Zhu,Panpan Dong,Hui Gong,Yunkun Wu

doi:10.3389/fimmu.2021.644396

Abstract

The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.

Highlights

Aquaculture has grown rapidly in the 21st century due to human population growth and declining marine capture in wild fisheries
The results demonstrated that the oral vaccine mesoporous silica nanoparticles (MSN)-dihydrolipoamide dehydrogenase (DLDH)@HP55 prepared in this study had good immunoprotective effects against Vibrio alginolyticus
Our results showed that the MSN-DLDH carrier system could transfer DLDH antigen to the intestinal tract of large yellow croaker by oral administration, eliciting an immune response and producing specific antibodies against Vibrio alginolyticus

Summary

Introduction

Aquaculture has grown rapidly in the 21st century due to human population growth and declining marine capture in wild fisheries. The most prevalent diseases affecting large yellow croaker are white-gill disease, vibriosis, iridovirus disease, etc., with diseases caused by bacteria being the most serious due to their high incidence and wide epidemic proportions [3,4,5]. This has threatened and challenged the aquaculture industry and food safety. The use of vaccines can reduce the risk of infection from viruses, bacteria, or parasites, reducing economic losses while ensuring the healthy development of fish farming and maintaining food safety. The design of high-performance, cost-effective, and stable vaccines with better release kinetics have tremendous application prospects

Methods

Results

Conclusion