Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles

Zhengrong Cui, Jigna Patel, Marina Tuzova, Phillip Ray, Ryan Phillips, Jerold G. Woodward, Avindra Nath, Russell J. Mumper

Research output: Contribution to journalArticlepeer-review

Abstract

A significant emphasis has been placed on the development of adjuvants and/or delivery systems to improve both antibody production and cell-mediated immune responses. We previously reported on a novel anionic nanoparticle, which led to enhanced humoral and T helper type-1 (Th1) biased immune responses in mice when coated with cationized model antigen. Tat (1-72) is a conserved regulatory HIV-1 protein. It was hypothesized that HIV vaccine strategies employing Tat (1-72) may be a promising approach. Although previous reports have suggested that Tat (1-86) may be immunosuppressive, it was demonstrated in this present study that Tat (1-72) was not immunosuppressive when co-administered to mice with ovalbumin (OVA). Tat (1-72) was coated on novel anionic nanoparticles. BALB/c mice were immunized with Tat (5 μg)-coated nanoparticles (15 μg) by subcutaneous injection on days 0 and 14. Antibody and cytokine release were determined on day 28 and compared to Tat (5 μg) adjuvanted with Alum (15 μg) as a Th2 control, Tat (5 μg) adjuvanted with Lipid A (50 μg) as a Th1 control. Immunization of BALB/c mice with Tat-coated nanoparticles resulted in antibody levels (IgG and IgM) comparable to those elicited from Tat and Alum. However, Tat-coated nanoparticles led to a Th1 biased immune response. The IFN-γ release from splenocytes with Tat-coated nanoparticles was comparable to that from mice immunized with Tat and Lipid A, and 3.3-fold greater than that from mice immunized with Tat and Alum. These studies warrant further investigation of these nanoparticles to enhance both antibody and cellular-based immune responses.

Original languageEnglish (US)
Pages (from-to)2631-2640
Number of pages10
JournalVaccine
Volume22
Issue number20
DOIs
StatePublished - Jun 30 2004

Keywords

  • AIDS
  • Cytokines
  • Rodent
  • Spleen and lymph nodes
  • Th1/Th2 cells
  • Vaccination

ASJC Scopus subject areas

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

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