Strong CD8+ T cell antigenicity and immunogenicity of large foreign proteins incorporated in HIV-1 VLPs able to induce a Nef-dependent activation/maturation of dendritic cells

A. Sistigu, L. Bracci, M. Valentini, E. Proietti, R. Bona, D. R M Negri, A. R. Ciccaglione, E. Tritarelli, R. Nisini, M. Equestre, A. Costantino, C. Marcantonio, S. M. Santini, C. Lapenta, S. Donati, P. Tataseo, M. Miceli, A. Cara, M. Federico

Research output: Contribution to journalArticle

Abstract

Virus-like particles (VLPs) are excellent tools for vaccines against pathogens and tumors. They can accommodate foreign polypeptides whose incorporation efficiency and immunogenicity however decrease strongly with the increase of their size. We recently described the CD8+ T cell immune response against a small foreign antigen (i.e., the 98 amino acid long human papilloma virus E7 protein) incorporated in human immunodeficiency virus (HIV)-1 based VLPs as product of fusion with an HIV-1 Nef mutant (Nefmut). Here, we extended our previous investigations by testing the antigenic/immunogenic properties of Nefmut-based VLPs incorporating much larger heterologous products, i.e., human hepatitis C virus (HCV) NS3 and influenza virus NP proteins, which are composed of 630 and 498 amino acids, respectively. We observed a remarkable cross-presentation of HCV NS3 in dendritic cells challenged with Nefmut-NS3 VLPs, as detected using a NS3 specific CD8+ T cell clone as well as PBMCs from HCV infected patients. On the other hand, when injected in mice, Nefmut-NP VLPs elicited strong anti-NP CD8+ T cell and CTL immune responses. In addition, we revealed the ability of Nefmut incorporated in VLPs to activate and mature primary human immature dendritic cells (iDCs). This phenomenon correlated with the activation of Src tyrosine kinase-related intracellular signaling, and can be transmitted from VLP-challenged to bystander iDCs. Overall, these results prove that Nefmut-based VLPs represent a rather flexible platform for the design of innovative CD8+ T cell vaccines.

Original languageEnglish
Pages (from-to)3465-3475
Number of pages11
JournalVaccine
Volume29
Issue number18
DOIs
Publication statusPublished - Apr 18 2011

Keywords

  • Cross-presentation
  • CTLs
  • Dendritic cells
  • Nef
  • Src tyrosine kinases
  • VLPs

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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  • Cite this

    Sistigu, A., Bracci, L., Valentini, M., Proietti, E., Bona, R., Negri, D. R. M., Ciccaglione, A. R., Tritarelli, E., Nisini, R., Equestre, M., Costantino, A., Marcantonio, C., Santini, S. M., Lapenta, C., Donati, S., Tataseo, P., Miceli, M., Cara, A., & Federico, M. (2011). Strong CD8+ T cell antigenicity and immunogenicity of large foreign proteins incorporated in HIV-1 VLPs able to induce a Nef-dependent activation/maturation of dendritic cells. Vaccine, 29(18), 3465-3475. https://doi.org/10.1016/j.vaccine.2011.02.059