Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses.

Luping Du,Wanzhe Yuan,Kongwang He,Fengjiao Pang,Bin Li,Xiangwei Xu,Zhengyu Yu,Aihua Mao

doi:10.3389/fcimb.2018.00007

Abstract

Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

Highlights

Porcine reproductive and respiratory syndrome (PRRS) is one of the viral diseases causing devastating economic losses to the swine industry worldwide (Du et al, 2013)
We successfully developed a porcine reproductive and respiratory syndrome virus (PRRSV) DNA vaccine entrapped in PLGA NPs modified with Ulex europaeus agglutinin 1 (UEA-1) (UEA1/PLGA-SynORF5)
It was reported that porous PLGA NPs coated with microfold cells (M cells) homing peptide-coupled chitosan was a promising approach for the oral delivery of BmpB vaccine against swine dysentery (SD) with successful stimulation of specific IgG in serum and sIgA in feces and intestine (Jiang et al, 2014)

Summary

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is one of the viral diseases causing devastating economic losses to the swine industry worldwide (Du et al, 2013). The causative agent, porcine reproductive and respiratory syndrome virus (PRRSV), infects pigs mainly through mucosal surfaces. Commercial PRRSV vaccines including killed and modified live vaccines are available. Commercial PRRSV vaccines are administrated through intramuscular immunization (i.m.), which fails to induce efficient mucosal immune responses to prevent PRRSV entry through mucosal surfaces. Nps prepared from PLGA containing hepatitis B virus, rotavirus, influenza virus, and parainfluenza virus delivered to mucosal sites in mice have been shown to generate a protective immune response (Thomas et al, 2011). A PLGA-entrapped PRRSV vaccine has been demonstrated to significantly increase immune responses and protection (Dwivedi et al, 2013; Binjawadagi et al, 2014a,b)

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Conclusion