E2 multimeric scaffold for vaccine formulation: Immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells

Maria Trovato, Francesco Maurano, Luciana D'Apice, Valerio Costa, Rossella Sartorius, Fausta Cuccaro, Sean P. McBurney, Shelly J. Krebs, Antonella Prisco, Alfredo Ciccodicola, Mauro Rossi, Nancy Haigwood, Piergiuseppe De Berardinis

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Background: The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. Results: The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4+ and CD8+ cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. Conclusions: The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

    Original languageEnglish (US)
    Article number152
    JournalBMC Microbiology
    Volume16
    Issue number1
    DOIs
    StatePublished - Jul 16 2016

    Fingerprint

    Transcriptome
    Dendritic Cells
    Vaccines
    Cytokines
    RNA Sequence Analysis
    Antigens
    Intranasal Administration
    Mucosal Immunity
    Th2 Cells
    Humoral Immunity
    Helper-Inducer T-Lymphocytes
    Cellular Immunity
    Immunoglobulin A
    Antibody Formation
    HIV-1
    Immunization
    Glycoproteins
    Mucous Membrane
    Vaccination
    Up-Regulation

    Keywords

    • Bone marrow-derived dendritic cells
    • E2 scaffold
    • Mucosal immunity
    • RNA-Sequencing
    • Th2
    • Transcriptome profile
    • Vaccine

    ASJC Scopus subject areas

    • Microbiology
    • Microbiology (medical)

    Cite this

    E2 multimeric scaffold for vaccine formulation : Immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells. / Trovato, Maria; Maurano, Francesco; D'Apice, Luciana; Costa, Valerio; Sartorius, Rossella; Cuccaro, Fausta; McBurney, Sean P.; Krebs, Shelly J.; Prisco, Antonella; Ciccodicola, Alfredo; Rossi, Mauro; Haigwood, Nancy; De Berardinis, Piergiuseppe.

    In: BMC Microbiology, Vol. 16, No. 1, 152, 16.07.2016.

    Research output: Contribution to journalArticle

    Trovato, M, Maurano, F, D'Apice, L, Costa, V, Sartorius, R, Cuccaro, F, McBurney, SP, Krebs, SJ, Prisco, A, Ciccodicola, A, Rossi, M, Haigwood, N & De Berardinis, P 2016, 'E2 multimeric scaffold for vaccine formulation: Immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells', BMC Microbiology, vol. 16, no. 1, 152. https://doi.org/10.1186/s12866-016-0772-x
    Trovato, Maria ; Maurano, Francesco ; D'Apice, Luciana ; Costa, Valerio ; Sartorius, Rossella ; Cuccaro, Fausta ; McBurney, Sean P. ; Krebs, Shelly J. ; Prisco, Antonella ; Ciccodicola, Alfredo ; Rossi, Mauro ; Haigwood, Nancy ; De Berardinis, Piergiuseppe. / E2 multimeric scaffold for vaccine formulation : Immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells. In: BMC Microbiology. 2016 ; Vol. 16, No. 1.
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    abstract = "Background: The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. Results: The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4+ and CD8+ cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. Conclusions: The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.",
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    AU - Trovato, Maria

    AU - Maurano, Francesco

    AU - D'Apice, Luciana

    AU - Costa, Valerio

    AU - Sartorius, Rossella

    AU - Cuccaro, Fausta

    AU - McBurney, Sean P.

    AU - Krebs, Shelly J.

    AU - Prisco, Antonella

    AU - Ciccodicola, Alfredo

    AU - Rossi, Mauro

    AU - Haigwood, Nancy

    AU - De Berardinis, Piergiuseppe

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    N2 - Background: The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. Results: The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4+ and CD8+ cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. Conclusions: The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

    AB - Background: The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. Results: The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4+ and CD8+ cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. Conclusions: The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

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    KW - E2 scaffold

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    KW - Vaccine

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