Mucosal vaccination with a codon-optimized hemagglutinin gene expressed by attenuated Salmonella elicits a protective immune response in chickens against highly pathogenic avian influenza

Liljebjelke, Karen; Petkov, Daniel; Kapczynski, Darrell R.

doi:10.1016/j.vaccine.2010.04.009

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…The currently-used antityphoid fever vaccine is derived from an attenuated Salmonella strain [46, 47]. Second, in the poultry industry, attenuated Salmonella vaccines might have unique potential for anti-influenza application, where inexpensive mass immunization can be achieved through drinking water or spray cabinet administration [48]. Finally, Salmonella -based vectors are highly immunogenic in inducing both innate and adaptive immune responses, due to the bacteria-encoded surface antigens such as lipopolysaccharide (LPS), and therefore can enhance the antigen-specific immune responses induced by the expression of the viral proteins [46, 49].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Thus, development of an effective vaccine is necessary to protect poultry and minimize human infections. Several approaches, including live attenuation and inactivation, have been carried out to develop a vaccine capable of protecting poultry from infection by H5N1 or H9N2 viruses 28–43 . An attractive approach for the vaccination of poultry would be a live attenuated vaccine, which can be inoculated on a large scale, and induces IgA antibodies that are important for mucosal immunity.…”

Section: Introductionmentioning

confidence: 99%

Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses

Nang¹,

Song²,

Kang³

et al. 2012

Influenza Resp Viruses

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Please cite this paper as: Nang et al. (2013) Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses. Influenza and Other Respiratory Viruses 7(2) 120–131. Background The highly pathogenic H5N1 and H9N2 influenza viruses are endemic in many countries around the world and have caused considerable economic loss to the poultry industry. Objectives We aimed to study whether a live attenuated H5N1 vaccine comprising internal genes from a cold‐adapted H9N2 influenza virus could protect chickens from infection by both H5N1 and H9N2 viruses. Methods We developed a cold‐adapted H9N2 vaccine virus expressing hemagglutinin and neuraminidase derived from the highly pathogenic H5N1 influenza virus using reverse genetics. Results and Conclusions Chickens immunized with the vaccine were protected from lethal infections with homologous and heterologous H5N1 or H9N2 influenza viruses. Specific antibody against H5N1 virus was detected up to 11 weeks after vaccination (the endpoint of this study). In vaccinated chickens, IgA and IgG antibody subtypes were induced in lung and intestinal tissue, and CD4+ and CD8+ T lymphocytes expressing interferon‐gamma were induced in the splenocytes. These data suggest that a live attenuated H5N1 vaccine with cold‐adapted H9N2 internal genes can protect chickens from infection with H5N1 and H9N2 influenza viruses by eliciting humoral and cellular immunity.

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“…A/Whooper Swan/Mongolia/3/05 (H5N1; H5MNG) is an HPAI H5N1 virus with the multibasic sequence in the HA protein [21]. A/Duck/Hokkaido/Vac-3/07 (H5N1; Vac3) is a low pathogenic H5N1 virus generated by the genetic reassortment of two low pathogenic avian influenza viruses [22].…”

Section: Resultsmentioning

confidence: 99%

Isolation of Recombinant Phage Antibodies Targeting the Hemagglutinin Cleavage Site of Highly Pathogenic Avian Influenza Virus

et al. 2013

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Highly pathogenic avian influenza (HPAI) H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS) in the hemagglutinin protein (HA). Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

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Mucosal vaccination with a codon-optimized hemagglutinin gene expressed by attenuated Salmonella elicits a protective immune response in chickens against highly pathogenic avian influenza

Cited by 18 publications

References 28 publications

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

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

Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses

Isolation of Recombinant Phage Antibodies Targeting the Hemagglutinin Cleavage Site of Highly Pathogenic Avian Influenza Virus

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