Protective immunity against influenza virus challenge by norovirus P particle-M2e and HA2-AtCYN vaccines in chickens

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

doi:10.1016/j.vaccine.2019.08.082

Cited by 10 publications

(8 citation statements)

References 69 publications

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“…M2e and LAH peptides are poorly immunogenic per se. Therefore, they have to be administered in association with adjuvant/delivery systems to induce robust immune responses in the host, including ligands of PRRs, bacterial toxins and derivatives, lipid-based particles, virus-like particles, organic and inorganic polymers and bacterial or viral vectored vaccines (5,(7)(8)(9)(10)(11)(12)(13)(14)(15). In this study, we have used innovative nanostructures developed in our research unit named "nanorings" as a mucosal vaccine delivery platform.…”

Section: Discussionmentioning

confidence: 99%

“…Owing to the high variability of IAV, an active area of research focuses on developing subunit vaccines containing conserved "universal" viral antigens, including epitopes located in the membrane proximal stalk domain of HA (HA2) and the ectodomain of the matrix protein 2 (M2e) (4,(6)(7)(8). Multiple vaccine candidates and platforms incorporating HA2 and/or M2e epitopes are under development, including fusion proteins with bacterial enterotoxins, flagellin, Neisseria meningititis outer membrane protein complex or Mycobacterium tuberculosis heat-shock protein 70, virus-like particles, bacterial outer membrane vesicles, bacteriophages, liposomes, immune stimulating complexes (ISCOM), bacterial or viral vectored vaccines, DNA or RNA vaccines, organic polymers such as chitosan, poly(lactic-co-glycolic acid) or poly-g-glutamic acid particles and inorganic nanoparticles such as gold nanoparticles (5,(7)(8)(9)(10)(11)(12)(13)(14)(15). These vaccine candidates were shown to provide protection against homologous and/or heterologous IAV challenges in pre-clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…The protective potential of HA2-and M2e-based vaccines also correlates with the generation of specific cell-mediated immune responses (7,8). Although vaccine trials with HA2-or M2ebased formulations gave encouraging results in mouse or ferret models, inconsistent results have been obtained in poultry (5,9,11,12,(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens

et al. 2021

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Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal formulations incorporating conserved IAV epitopes, namely the long alpha helix (LAH) of the stalk domain of hemagglutinin and three tandem repeats of the ectodomain of the matrix protein 2 (3M2e), as universal mucosal anti-IAV vaccines in mice and chickens. The IAV epitopes were grafted to nanorings, a novel platform technology for mucosal vaccination formed by the nucleoprotein (N) of the respiratory syncytial virus, in fusion or not with the C-terminal end of the P97 protein (P97c), a recently identified Toll-like receptor 5 agonist. Fusion of LAH to nanorings boosted the generation of LAH-specific systemic and local antibody responses as well as cellular immunity in mice, whereas the carrier effect of nanorings was less pronounced towards 3M2e. Mice vaccinated with chimeric nanorings bearing IAV epitopes in fusion with P97c presented modest LAH- or M2e-specific IgG titers in serum and were unable to generate a mucosal humoral response. In contrast, N-3M2e or N-LAH nanorings admixed with Montanide™ gel (MG) triggered strong specific humoral responses, composed of serum type 1/type 2 IgG and mucosal IgG and IgA, as well as cellular responses dominated by type 1/type 17 cytokine profiles. All mice vaccinated with the [N-3M2e + N-LAH + MG] formulation survived an H1N1 challenge and the combination of both N-3M2e and N-LAH nanorings with MG enhanced the clinical and/or virological protective potential of the preparation in comparison to individual nanorings. Chickens vaccinated parenterally or mucosally with N-LAH and N-3M2e nanorings admixed with Montanide™ adjuvants developed a specific systemic humoral response, which nonetheless failed to confer protection against heterosubtypic challenge with a highly pathogenic H5N8 strain. Thus, while the combination of N-LAH and N-3M2e nanorings with Montanide™ adjuvants shows promise as a universal mucosal anti-IAV vaccine in the mouse model, further experiments have to be conducted to extend its efficacy to poultry.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens

et al. 2021

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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%

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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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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Norovirus

Lindesmith¹,

Verardi²,

Mallory³

et al. 2023

Plotkin's Vaccines

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Protective immunity against influenza virus challenge by norovirus P particle-M2e and HA2-AtCYN vaccines in chickens

Cited by 10 publications

References 69 publications

Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens

Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens

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

Norovirus

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