Intracellular delivery of HA1 subunit antigen through attenuated Salmonella Gallinarum act as a bivalent vaccine against fowl typhoid and low pathogenic H5N3 virus

Nitin Machindra Kamble,John Hwa Lee,Kim Je Hyoung

doi:10.1186/s13567-017-0446-1

Nitin Machindra Kamble, John Hwa Lee + Show 1 more

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https://doi.org/10.1186/s13567-017-0446-1

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Journal: Veterinary Research	Publication Date: Aug 7, 2017
Citations: 2	License type: open-access

Affiliation: Jeonbuk National University

Abstract

Introduction of novel inactivated oil-emulsion vaccines against different strains of prevailing and emerging low pathogenic avian influenza (LPAI) viruses is not an economically viable option for poultry. Engineering attenuated Salmonella Gallinarum (S. Gallinarum) vaccine delivering H5 LPAI antigens can be employed as a bivalent vaccine against fowl typhoid and LPAI viruses, while still offering economic viability and sero-surveillance capacity. In this study, we developed a JOL1814 bivalent vaccine candidate against LPAI virus infection and fowl typhoid by engineering the attenuated S. Gallinarum to deliver the globular head (HA1) domain of hemagglutinin protein from H5 LPAI virus through pMMP65 constitutive expression plasmid. The important feature of the developed JOL1814 was the delivery of the HA1 antigen to cytosol of peritoneal macrophages. Immunization of chickens with JOL1814 produced significant level of humoral, mucosal, cellular and IL-2, IL-4, IL-17 and IFN-γ cytokine immune response against H5 HA1 and S. Gallinarum antigens in the immunized chickens. Post-challenge, only the JOL1814 immunized chicken showed significantly faster clearance of H5N3 virus in oropharyngeal and cloacal swabs, and 90% survival rate against lethal challenge with a wild type S. Gallinarum. Furthermore, the JOL1814 immunized were differentiated from the H5N3 LPAI virus infected chickens by matrix (M2) gene-specific real-time PCR. In conclusion, the data from the present showed that the JOL1814 can be an effective bivalent vaccine candidate against H5N3 LPAI and fowl typhoid infection in poultry while still offering sero-surveillance property against H5 avian influenza virus.

Highlights

In vitro delivery of HA1 antigen through JOL1814 to peritoneal macrophages The in vitro macrophage invasion assay was performed to assess the delivery of the expressed HA1 proteins by JOL1814
A strain matched and cost-effective vaccine against different H5 subtypes of low pathogenic avian influenza (LPAI) viruses with differentiate between vaccinated and infected birds (DIVA) capacity is needed to control LPAI virus outbreaks and prevent emergence of high-pathogenicity avian influenza (HPAI) viruses [3, 7]
Gallinarum mutant, a balanced-lethal host-vector system was previously constructed by deletion of the aspartate-semialdehyde dehydrogenase from wild-type strain and which can be functionally complemented with Asd+ plasmid [29]

Summary

Introduction

Gallinarum) and avian influenza virus (AIV) are two contagious and infectious pathogens that are responsible for severe economic distress in poultry production [1, 2]. S. Gallinarum, an etiological agent of fowl typhoid (FT), causes a severe systemic disease with a high mortality rate in chickens. Infection of chickens with AIV causes either a mortality or respiratory distress with serious complications depending on the pathogenicity of the infecting virus [1, 2]. AIV is categorized as high-pathogenicity avian influenza (HPAI) or low-pathogenicity

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