Heterosubtypic protection against avian influenza virus by live attenuated and chimeric norovirus P-particle-M2e vaccines in chickens

Ghorbani, Amir; Ngunjiri, John M.; Xia, Ming; Elaish, Mohamed; Jang, Hyesun; Kc, Mahesh; Abundo, Michael C.; Jiang, Xi; Lee, Chang-Won

doi:10.1016/j.vaccine.2019.01.037

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…Administration of analgesia drugs was unnecessary since the birds were euthanized soon after the emergence of clinical symptoms. Humane euthanasia was actualized by exposure to carbon dioxide (CO 2 ) as previously described ( Elaish et al, 2017 ; Elaish et al, 2019 ; Ghorbani et al, 2019 ; Jang et al, 2018 ). Three poults were placed in the euthanasia chamber connected to a CO 2 source, with CO 2 flow set at 10–30% displacement of chamber volume/minute.…”

Section: Methodsmentioning

confidence: 99%

“…Birds were observed for respiratory arrest and lack of heartbeat and the CO 2 flow was maintained for at least one minute after the respiratory arrest and lack of heartbeat were observed. Upon observation of death, an additional secondary physical euthanasia (cervical dislocation or removal of a vital organ) was performed before collection of tissues and carcass disposal ( Elaish et al, 2017 ; Elaish et al, 2019 ; Ghorbani et al, 2019 ; Jang et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

“…Viral RNA (vRNA) was extracted from 200 µL of supernatant using RNeasy Mini Kit (Qiagen Sciences Inc., Germantown, MD, USA). The amount of viral genomes was determined using quantitative reverse transcription PCR (qRT-PCR) with type A influenza virus matrix gene specific primers and probes, and EID 50 viral titers were extrapolated from standard curves generated with the stocks used for infection as described in our previous reports ( Ghorbani et al, 2019 ; Jang, Ngunjiri & Lee, 2016 ). To generate a standard curve, viral RNA was extracted from serial 10-fold dilutions of the same virus stock (with known EID 50 titer) used to inoculate the turkeys and subjected to qRT-PCR to generate cycle threshold (Ct) values.…”

Section: Methodsmentioning

confidence: 99%

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Influenza A virus infection in turkeys induces respiratory and enteric bacterial dysbiosis correlating with cytokine gene expression

Ngunjiri

Taylor

et al. 2021

PeerJ

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Turkey respiratory and gut microbiota play important roles in promoting health and production performance. Loss of microbiota homeostasis due to pathogen infection can worsen the disease or predispose the bird to infection by other pathogens. While turkeys are highly susceptible to influenza viruses of different origins, the impact of influenza virus infection on turkey gut and respiratory microbiota has not been demonstrated. In this study, we investigated the relationships between low pathogenicity avian influenza (LPAI) virus replication, cytokine gene expression, and respiratory and gut microbiota disruption in specific-pathogen-free turkeys. Differential replication of two LPAI H5N2 viruses paralleled the levels of clinical signs and cytokine gene expression. During active virus shedding, there was significant increase of ileal and nasal bacterial contents, which inversely corresponded with bacterial species diversity. Spearman’s correlation tests between bacterial abundance and local viral titers revealed that LPAI virus-induced dysbiosis was strongest in the nasal cavity followed by trachea, and weakest in the gut. Significant correlations were also observed between cytokine gene expression levels and relative abundances of several bacteria in tracheas of infected turkeys. For example, interferon γ/λ and interleukin-6 gene expression levels were correlated positively with Staphylococcus and Pseudomonas abundances, and negatively with Lactobacillus abundance. Overall, our data suggest a potential relationship where bacterial community diversity and enrichment or depletion of several bacterial genera in the gut and respiratory tract are dependent on the level of LPAI virus replication. Further work is needed to establish whether respiratory and enteric dysbiosis in LPAI virus-infected turkeys is a result of host immunological responses or other causes such as changes in nutritional uptake.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Influenza A virus infection in turkeys induces respiratory and enteric bacterial dysbiosis correlating with cytokine gene expression

Ngunjiri

Taylor

et al. 2021

PeerJ

Self Cite

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“…Basically, in a prime-boost immunization strategy, the first dose of vaccine is given followed In addition, the M2 protein is produced abundantly and presented readily on the surface of infected host cells [70,79,80]. In experimental models such as BALB/c mice and chickens, anti-M2e antibodies bind strongly to the surface-bound M2e, thereby inhibiting virus replication and budding from infected cells [79,[81][82][83]. The binding of antibodies to M2e protein also promotes removal of infected lung epithelial cells via complement lysis or antibody-dependent cell cytotoxicity (ADCC) [84].…”

Section: M2e As Immunogenmentioning

confidence: 99%

M2e-Based Influenza Vaccines with Nucleoprotein: A Review

Tan

Alitheen

et al. 2021

Vaccines

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Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as Escherichia coli without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.

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“…Despite the presence of the invariant domain of M2, antibody responses to M2 are insufficient after vaccination, indicating that M2 is poorly immunogenic [ 7 ]. To enhance the immunogenicity of M2e, some strategies have been reported for immunization with M2e peptide fusion constructs linked to carrier vehicles as vaccine candidates, which have been shown to have safety issues but provide protection against lethal infection in chickens [ 8 , 9 ]. However, these M2e vaccine candidates provide limited protection against lethal challenge, as shown by significant weight loss and signs of disease, even in the presence of potent adjuvants, such as heat-labile endotoxin or cholera toxin, Freund adjuvants, or bacterial protein conjugates [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Protective immunity induced by oral vaccination with a recombinant Lactococcus lactis vaccine against H5Nx in chickens

Ren

Yang

et al. 2022

BMC Vet Res

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Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.

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Heterosubtypic protection against avian influenza virus by live attenuated and chimeric norovirus P-particle-M2e vaccines in chickens

Cited by 17 publications

References 41 publications

Influenza A virus infection in turkeys induces respiratory and enteric bacterial dysbiosis correlating with cytokine gene expression

Influenza A virus infection in turkeys induces respiratory and enteric bacterial dysbiosis correlating with cytokine gene expression

M2e-Based Influenza Vaccines with Nucleoprotein: A Review

Protective immunity induced by oral vaccination with a recombinant Lactococcus lactis vaccine against H5Nx in chickens

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