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Intranasal administration of inactivated avian influenza virus of H5N1 subtype vaccine-induced systemic immune response in chicken and mice.

ABSTRACT: Aim:The need for non-parenteral administration of inactivated avian influenza virus of H5N1 subtype (AIV-H5N1) vaccine is paramount. Here, we provide preliminary data on the immune response of chicken and mice after intranasal administration of AIV-H5N1-inactivated vaccine with ISCOMS, Inmunair (INM), and combined ISCOMS and INM as an adjuvant. Materials and Methods:The AIV isolate of A/Chicken/Denpasar/01/2004 (H5N1) was cultivated in specific pathogen-free chicken eggs and inactivated with formaldehyde. The vaccine preparation was added with those adjuvants for intranasal administration and aluminum hydroxide for subcutaneous injection. The chicken and mouse were vaccinated at the age of 3 weeks or 1 month and repeated 2 weeks thereafter. In one experiment, chicken was injected with Newcastle disease virus (NDV) at the same time with AIV vaccine. The sera were collected at one (serum 1) and 2 w (serum 2) after booster vaccination. The anti-AIV-H5 and NDV antibodies in chicken sera were detected using hemagglutination inhibition (HI) assay. Mouse IgG anti-AIV-H5N1 antibody was detected using ELISA. Results:The result shows that the geometric mean titers (GMTs) of chicken sera of intranasal vaccinated with inactivated AIV-H5N1 vaccine with mixed ISCOM- INM as adjuvant were <20.0 and 22.7 unit HI-unit (HIU) in serum 1 and serum 2, respectively. The GMTs of the positive control group were 23.7 and 25.7 HIU in serum 1 and serum 2, respectively. The result of the second experiment shows that IgG anti-AIV-H5N1 was detected in mouse sera. In the third experiment, the GMTs of anti-NDV in chicken vaccinated subsequently with inactivated NDV vaccine and AIV-H5N1 with mixed ISCOMS-INM administrated intranasally and aluminum hydroxide adjuvant administrated through subcutaneous injection as well as positive control group receiving NDV vaccine only were 28.0, 28.0, and 27.4 HIU in serum 1 while were 29.6, 29.2, and 28.2 HIU in serum 2, respectively. Conclusion:Intranasal administration of inactivated AIV-H5N1 vaccine-induced a systemic immune response in chicken and mice after adding ISCOMS and/or INM as adjuvants. The adjuvant and the intranasal administration caused no immunosuppressive effect on the chicken immune response to NDV vaccine.

SUBMITTER: Suartha IN

PROVIDER: S-EPMC5891878 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Intranasal administration of inactivated avian influenza virus of H5N1 subtype vaccine-induced systemic immune response in chicken and mice.

Suartha I N IN Suartini G A A GAA Wirata I W IW Dewi N M A R K NMARK Putra G N N GNN Kencana G A Y GAY Mahardika G N GN

Veterinary world 20180220 2

<h4>Aim</h4>The need for non-parenteral administration of inactivated avian influenza virus of H5N1 subtype (AIV-H5N1) vaccine is paramount. Here, we provide preliminary data on the immune response of chicken and mice after intranasal administration of AIV-H5N1-inactivated vaccine with ISCOMS, Inmunair (INM), and combined ISCOMS and INM as an adjuvant.<h4>Materials and methods</h4>The AIV isolate of A/Chicken/Denpasar/01/2004 (H5N1) was cultivated in specific pathogen-free chicken eggs and inact ...[more]

PMID: 29657407

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Project description:H7N9 avian influenza virus (AIV) is an emerging zoonotic pathogen, and it is necessary to develop a differentiating infected from vaccinated animals (DIVA) vaccine for the purpose of eradication. H7N9 subtype AIV hemagglutinin subunit 2 glycoprotein (HA2) peptide chips and antisera of different AIV subtypes were used to screen H7N9 AIV-specific epitopes. A selected specific epitope in the HA2 protein of H7N9 AIV strain A/Chicken/Huadong/JD/17 (JD/17) was replaced with an epitope from an H3N2 subtype AIV strain by reverse genetics. The protection and serological DIVA characteristics of the recombinant H7N9 AIV strain were evaluated. The results showed that a specific epitope on the HA2 protein of H7N9 AIV, named the H7-12 peptide, was successfully screened. The recombinant H7N9 AIV with a modified epitope in the HA2 protein was rescued and named A/Chicken/Huadong/JD-cHA/17 (JD-cHA/17). The HA titer of JD-cHA/17 was 10 log2, and the 50% egg infective dose (EID50) titer was 9.67 log10 EID50/ml. Inactivated JD-cHA/17 induced a hemagglutination inhibition (HI) antibody titer similar that of the parent strain and provided 100% protection against high-pathogenicity or low-pathogenicity H7N9 AIV challenge. A peptide chip coated with H7-12 peptide was successfully applied to detect the seroconversion of chickens infected or vaccinated with JD/17, while there was no reactivity with antisera of chickens vaccinated with JD-cHA/17. Therefore, the marked vaccine candidate JD-cHA/17 can be used as a DIVA vaccine against H7N9 avian influenza when combined with an H7-12 peptide chip, making it a useful tool for stamping out the H7N9 AIV. IMPORTANCE DIVA vaccine is a useful tool for eradicating avian influenza, especially for highly pathogenic avian influenza. Several different DIVA strategies have been proposed for avian influenza inactivated whole-virus vaccine, involving the neuraminidase (NA), nonstructural protein 1 (NS1), matrix protein 2 ectodomain (M2e), or HA2 gene. However, virus reassortment, residual protein in a vaccine component, or reduced vaccine protection may limit the application of these DIVA strategies. Here, we constructed a novel chimeric H7N9 AIV, JD-cHA/17, that expressed the entire HA protein with substitution of an H3 AIV epitope in HA2. The chimeric H7N9 recombinant vaccine provides full clinical protection against high-pathogenicity or low-pathogenicity H7N9 AIV challenge. Combined with a short-peptide-based microarray chip containing the H7N9 AIV epitope in HA2, our finding is expected to be useful as a marker vaccine designed for avian influenza.

Project description:BACKGROUND:We developed a novel intranasal influenza vaccine approach that is based on the construction of replication-deficient vaccine viruses that lack the entire NS1 gene (DeltaNS1 virus). We previously showed that these viruses undergo abortive replication in the respiratory tract of animals. The local release of type I interferons and other cytokines and chemokines in the upper respiratory tract may have a "self-adjuvant effect", in turn increasing vaccine immunogenicity. As a result, DeltaNS1 viruses elicit strong B- and T- cell mediated immune responses. METHODOLOGY/PRINCIPAL FINDINGS:We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5:3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining genes were derived from IVR-116. The HA cleavage site was modified in a trypsin dependent manner, serving as the second attenuation factor in addition to the deleted NS1 gene. The vaccine candidate was able to grow in the Vero cells that were cultivated in a serum free medium to titers exceeding 8 log(10) TCID(50)/ml. The vaccine virus was replication deficient in interferon competent cells and did not lead to viral shedding in the vaccinated animals. The studies performed in three animal models confirmed the safety and immunogenicity of the vaccine. Intranasal immunization protected ferrets and mice from being infected with influenza H5 viruses of different clades. In a primate model (Macaca mulatta), one dose of vaccine delivered intranasally was sufficient for the induction of antibodies against homologous A/Vietnam/1203/04 and heterologous A/Indonesia/5/05 H5N1 strains. CONCLUSION/SIGNIFICANCE:Our findings show that intranasal immunization with the replication deficient H5N1 DeltaNS1 vaccine candidate is sufficient to induce a protective immune response against H5N1 viruses. This approach might be attractive as an alternative to conventional influenza vaccines. Clinical evaluation of DeltaNS1 pandemic and seasonal influenza vaccine candidates are currently in progress.

Project description:The highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world and has caused sporadic lethal infections in humans. Vaccines are important in HPAIV control both for poultry and in prepandemic preparedness for humans. This study assessed inactivated prepandemic vaccine strains in a One Health framework across human and agricultural and wildlife animal health, focusing on the genetic and antigenic diversity of field H5N1 Gs/GD viruses from the agricultural sector and assessing cross-protection in a chicken challenge model. Nearly half (47.92%) of the 48 combinations of vaccine and challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death times (MDT), and the virus-shedding titers were significantly lower than those of the sham-vaccinated group (P ≤ 0.05). The antibody titers in the prechallenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination-inhibiting (HI) antibodies against the homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters and homologous or closely related vaccine and challenge viruses gave the best prediction of protection. Through additional analysis, we identified a pattern of epitope substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV in the agricultural sector and for human prepandemic preparedness. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.IMPORTANCE The sustained circulation of highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 (Gs/GD) lineage in the agricultural sector and some wild birds has led to the evolution and selection of distinct viral lineages involved in escape from vaccine protection. Our results using inactivated vaccine candidates from the human pandemic preparedness program in a chicken challenge model identified critical antigenic conformational epitopes on H5 hemagglutinin (HA) from different clades that were associated with antibody recognition and escape. Even though other investigators have reported epitope mapping in the H5 HA, much of this information pertains to epitopes reactive to mouse antibodies. Our findings validate changes in antigenic epitopes of HA associated with virus escape from antibody neutralization in chickens, which has direct relevance to field protection and virus evolution. Therefore, knowledge of these immunodominant regions is essential to proactively develop diagnostic tests, improve surveillance platforms to monitor AIV outbreaks, and design more efficient and broad-spectrum agricultural and human prepandemic vaccines.

Dataset Information

Intranasal administration of inactivated avian influenza virus of H5N1 subtype vaccine-induced systemic immune response in chicken and mice.

Publications

Intranasal administration of inactivated avian influenza virus of H5N1 subtype vaccine-induced systemic immune response in chicken and mice.

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