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

Vaccine. 2007 Aug 10;25(32):5968-77. doi: 10.1016/j.vaccine.2007.05.052. Epub 2007 Jun 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Administration, Intranasal
  • Animals
  • Epitope Mapping
  • Epitopes, B-Lymphocyte / immunology
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp160 / immunology
  • HIV-1 / classification*
  • HIV-1 / immunology*
  • Immunity, Cellular / immunology*
  • Immunity, Mucosal / immunology*
  • Immunization, Secondary*
  • Immunoglobulin G / blood
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Spleen / cytology
  • Spleen / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*


  • AIDS Vaccines
  • Epitopes, B-Lymphocyte
  • HIV Antibodies
  • HIV Envelope Protein gp160
  • Immunoglobulin G
  • Vaccines, DNA