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

BMC Microbiology

Research Article

Shelly J. Krebs¹  Sean P. McBurney¹  Nancy L. Haigwood¹  Francesco Maurano²  Mauro Rossi²  Antonella Prisco³  Valerio Costa³  Alfredo Ciccodicola⁴  Luciana D’Apice⁵  Fausta Cuccaro⁵  Rossella Sartorius⁵  Maria Trovato⁵  Piergiuseppe De Berardinis⁵ 

[1] Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, 97006, Beaverton, OR, USA;Institute of Food Sciences, C.N.R, Via Roma 64, 83100, Avellino, Italy;Institute of Genetics and Biophysics A. Buzzati-Traverso, C.N.R, Via Pietro Castellino 111, 80131, Naples, Italy;Institute of Genetics and Biophysics A. Buzzati-Traverso, C.N.R, Via Pietro Castellino 111, 80131, Naples, Italy;Department of Science and Technology, University of Naples “Parthenope”, Centro Direzionale Site island C4, 80143, Naples, Italy;Institute of Protein Biochemistry, C.N.R, Via Pietro Castellino 111, 80131, Naples, Italy;

关键词: E2 scaffold;    Vaccine;    Mucosal immunity;    Bone marrow-derived dendritic cells;    RNA-Sequencing;    Transcriptome profile;    Th2;   

DOI  :  10.1186/s12866-016-0772-x

 received in 2016-01-19, accepted in 2016-07-12,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsThe 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s). 2016