Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection

Abstract

Attenuated strains of invasive enteric bacteria, such as Salmonella, represent promising gene delivery agents for nucleic acid-based vaccines as they can be administrated orally. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the hemagglutinin (HA) and neuraminidase (NA) of a highly pathogenic H5N1 influenza virus. We showed that the constructed Salmonella strain exhibited efficient gene transfer activity for HA and NA expression and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we evaluated the immune responses and protection induced by the constructed Salmonella-based vaccine. Our study showed that the Salmonella-based vaccine induced significant production of anti-HA serum IgG and mucosal IgA, and of anti-HA interferon-γ producing T cells in orally vaccinated mice. Furthermore, mice orally vaccinated with the Salmonella vaccine expressing viral HA and NA proteins were completely protected from lethal challenge of highly pathogenic H5N1 as well as H1N1 influenza viruses while none of the animals treated with the Salmonella vaccine carrying the empty expression vector with no viral antigen expression was protected. These results suggest that the Salmonella-based vaccine elicits strong antigen-specific humoral and cellular immune responses and provides effective immune protection against multiple strains of influenza viruses. Furthermore, our study demonstrates the feasibility of developing novel attenuated Salmonella strains as new oral vaccine vectors against influenza viruses.

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

“…These findings clearly indicate that Salmonella -based influenza vaccines can stimulate efficient Th1 type of immunity and can protect the hosts from pathogenic influenza infections. Our results are in agreement to the previously published reports [ 18 , 32 ].…”

“…In the present study, the Salmonella -based HA, NA and M2e vaccines not only generated efficient humoral responses but also stimulated high level of antigen-specific cellular responses. Previous study have shown that immunization with Salmonella -based HA and NA vaccination elicits efficient cellular immune responses and protects the mice against the homologous and heterologous H5N1 and H1N1 challenges, respectively [ 32 ]. Our results show that vaccinated PBMCs stimulated with recall inactivated H7N9 antigen resulted in higher proliferative responses compared to the control chickens.…”

Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens

“…Exploiting live attenuated Salmonella system to deliver IBV S1 immunogenic protein is a highly economical vaccination strategy that allows for a quick response to deployment of vaccines, as it circumvents the need for a constant supply of specific-pathogen-free (SPF) embryonated eggs. Furthermore, Salmonella -based vaccination strategy induces efficient antigen-specific humoral and cell-mediated immunity [ 17 – 19 ], and these vaccines have already been approved for use in poultry [ 20 ]. Herein, we show that attenuated SG mutant delivering immunogenic S1 protein elicited efficient IBV-specific humoral and cell-mediated immune (CMI) responses and conferred significant protection against a virulent IBV challenge.…”

A consensus-hemagglutinin-based vaccine delivered by an attenuated Salmonella mutant protects chickens against heterologous H7N1 influenza virus

“…Therefore, influenza vaccines need to be annually updated pertaining to the antigenic changes of circulating field strains. Live bacterial vectors are a promising approach to deliver immunogenic proteins of AIV to the immune system [21]. Studies have demonstrated that attenuated Salmonella based system carrying various heterologous viral antigens elicit efficient systemic and mucosal immune responses [22].…”