DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity

L. Buonaguro, C. Devito, M. L. Tornesello, U. Schröder, B. Wahren, J. Hinkula, F. M. Buonaguro

Research output: Contribution to journalArticlepeer-review

Abstract

The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.

Original languageEnglish
Pages (from-to)5968-5977
Number of pages10
JournalVaccine
Volume25
Issue number32
DOIs
Publication statusPublished - Aug 10 2007

Keywords

  • HIV-1
  • Humoral immunity
  • Mucosal adjuvants
  • Mucosal response
  • Prime-boost approach
  • Virus-like particles (VLP)

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity'. Together they form a unique fingerprint.

Cite this