Immunization with gp120-depleted whole killed HIV immunogen and a second-generation CpG DNA elicits strong HIV-specific responses in mice

Daria Trabattoni, Alberto Clivio, Dorothy H. Bray, Lakshmi Bhagat, Silvia Beltrami, Giada Maffeis, Eugenio Cesana, Peter Lowry, Francesca Lissoni, Ekambar R. Kandimalla, Timothy Sullivan, Sudhir Agrawal, Richard Bartholomew, Mario Clerici

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 Immunogen is a gp120-depleted whole killed virus vaccine candidate formulated with Incomplete Freund's Adjuvant (HIV-IFA). We evaluated in a mouse model the immunogenicity of HIV-IFA by itself and when combined with HYB2055, an immunomodulatory oligonucleotide consisting of a novel DNA structure and synthetic CpR immunostimulatory motif, as an adjuvant. C57/BL6 mice were immunized with HIV-IFA alone or combined with HYB2055. Mice treated with HYB2055 or with PBS were used as controls. Compared to HIV-IFA alone, immunization with HIV-IFA and HYB2055 combination elicited strong production of HIV- and p24-specific IFNγ, RANTES, MIP 1α, and MIP 1β, as well as high titers of HIV- and p24-specific antibodies. Inclusion of HYB2055 also reduced levels of IL-5 produced by HIV-IFA alone. HYB2055 enhances the immunogenicity of HIV-IFA and shifts responses towards a type 1 cytokine profile. The immune enhancing effects of HYB2055 adjuvant were dose-dependent. These findings warrant clinical evaluation of the HIV-1 immunogen/HYB2055 candidate as a therapeutic vaccine for HIV-1 infected patients.

Original languageEnglish
Pages (from-to)1470-1477
Number of pages8
JournalVaccine
Volume24
Issue number9
DOIs
Publication statusPublished - Feb 27 2006

Keywords

  • CpG
  • Cytokines
  • HIV
  • Immunology
  • Immunomodulatory oligonucleotide
  • TLR9
  • Vaccine

ASJC Scopus subject areas

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

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