Oral immunization with a novel attenuated Salmonella Typhimurium encoding influenza HA, M2e and NA antigens protects chickens against H7N9 infection

Je Hyoung Kim,Irshad Ahmed Hajam,John Hwa Lee

doi:10.1186/s13567-018-0509-y

Je Hyoung Kim, Irshad Ahmed Hajam + Show 1 more

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https://doi.org/10.1186/s13567-018-0509-y

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Journal: Veterinary Research	Publication Date: Feb 1, 2018
Citations: 18	License type: open-access

Affiliation: Jeonbuk National University

Abstract

Attenuated Salmonella strains constitute a promising technology for the development of efficient protein-based influenza vaccines. H7N9, a low pathogenic avian influenza (LPAI) virus, is a major public health concern and currently there are no effective vaccines against this subtype. Herein, we constructed a novel attenuated Salmonella Typhimurium strain for the delivery and expression of H7N9 hemagglutinin (HA), neuraminidase (NA) or the conserved extracellular domain of the matrix protein 2 (M2e). We demonstrated that the constructed Salmonella strains exhibited efficient HA, NA and M2e expressions, respectively, and the constructs were safe and immunogenic in chickens. Our results showed that chickens immunized once orally with Salmonella (Sal) mutants encoding HA (Sal-HA), M2e (Sal-M2e) or NA (Sal-NA), administered either alone or in combination, induced both antigen-specific humoral and cell mediated immune (CMI) responses, and protected chickens against the lethal H7N9 challenge. However, chickens immunized with Sal-HA+Sal-M2e+Sal-NA vaccine constructs exhibited efficient mucosal and CMI responses compared to the chickens that received only Sal-HA, Sal-M2e or Sal-M2e+Sal-NA vaccine. Further, chickens immunized with Sal-HA+Sal-M2e+Sal-NA constructs cleared H7N9 infection at a faster rate compared to the chickens that were vaccinated with Sal-HA, Sal-M2e or Sal-M2e+Sal-NA, as indicated by the reduced viral shedding in cloacal swabs of the immunized chickens. We conclude that this vaccination strategy, based on HA, M2e and NA, stimulated efficient induction of immune protection against the lethal H7N9 LPAI virus and, therefore, further studies are warranted to develop this approach as a potential prophylaxis against LPAI viruses affecting poultry birds.

Highlights

Avian influenza viruses, classified as highly pathogenic avian influenza (HPAI) or low-pathogenicity avian influenza (LPAI), cause huge economical losses to the poultry industry annually [1, 2]
Our results show that chickens immunized once orally with Salmonella mutants encoding HA (Sal-HA), M2 ectodomain (M2e) (Sal-M2e) or NA (Sal-NA), administered either alone or in combination, induced both humoral and cell mediated immune (CMI) responses, and protected the chickens against the lethal H7N9 challenge
Our results further demonstrate that the chickens immunized with a co-mix of Salmonella mutants encoding HA, M2e or NA proteins showed higher protective immunity than the chickens vaccinated with Sal-HA, Sal-M2e or Sal-M2e+Sal-NA based vaccine

Summary

Introduction

Avian influenza viruses, classified as highly pathogenic avian influenza (HPAI) or low-pathogenicity avian influenza (LPAI), cause huge economical losses to the poultry industry annually [1, 2]. Outbreaks of HPAI and LPAI viruses belonging to H7 subtype in chickens have been reported in the past [3,4,5], and infections caused by H7N9 LPAI virus have infected poultry birds and humans as well, with limited person to person transmission [6, 7]. Humans infected with H7N9 virus mostly result in severe respiratory illness, with a mortality of roughly 30% [9]. Potent and effective vaccines must be available to prevent the occurrence of H7N9 infection in humans

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