Lipid nanocapsule as vaccine carriers for his-tagged proteins: Evaluation of antigen-specific immune responses to HIV i His-Gag p41 and systemic inflammatory responses

Saurabh Wadhwa, Anekant Jain, Jerold G. Woodward, Russell J. Mumper

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The purpose of this study was to design novel nanocapsules (NCs) with surface-chelated nickel (Ni-NCs) as a vaccine delivery system for histidine (His)-tagged protein antigens. Ni-NCs were characterized for binding His-tagged model proteins through high-affinity non-covalent interactions. The mean diameter and zeta potential of the optimized Ni-NCs were 214.9 nm and -14.8 mV, respectively. The optimal binding ratio of His-tagged Green Fluorescent Protein (His-GFP) and His-tagged HIV-1 Gag p41 (His-Gag p41) to the Ni-NCs was 1:221 and 1:480 w/w, respectively. Treatment of DC2.4 cells with Ni-NCs did not result in significant loss in the cell viability up to 24 h (<5%). We further evaluated the antibody response of the Ni-NCs using His-Gag p41 as a model antigen. Formulations were administered subcutaneously to BALB/c mice at day 0 (prime) and 14 (boost) followed by serum collection on day 28. Serum His-Gag p41-specific antibody levels were found to be significantly higher at 1 and 0.5 μg doses of Gag p41-His-Ni-NCs (His-Gag p41 equivalent) compared with His-Gag p41 (1 μg) adjuvanted with aluminum hydroxide (AH). The serum IgG2a levels induced by Gag p41-His-Ni-NCs (1 μg) were significantly higher than AH adjuvanted His-Gag p41. The Ni-NCs alone did not result in the elevation of systemic IL-12/p40 and CCL5/RANTES inflammatory cytokine levels upon subcutaneous administration in BALB/c mice. In conclusion, the proposed Ni-NCs can bind His-tagged proteins and have the potential to be used as antigen delivery system capable of generating strong antigen-specific antibodies at doses much lower than with aluminum-based adjuvant and causing no significant elevation of systemic pro-inflammatory IL-12/p40 and CCL5/RANTES cytokines.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume80
Issue number2
DOIs
StatePublished - Feb 2012

Bibliographical note

Funding Information:
The project described was supported by Award Number R01AI058842 to RJM and JW from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The authors would like to thank Dr. Robert Seder (Vaccine Research Center, NIH-NIAID) for kindly providing His-Gag p41 and Dr. Kenneth L. Rock (Department of Pathology, University of Massachusetts Medical School) for providing DC2.4 dendritic cells. The authors would also like to thank Dr. Sohrab Habibi of the Mass Spectrometry Facility, Michael Chua of the Michael Hooker Microscopy Facility, Todd Gambling of Environmental Protection Agency at the University of North Carolina at Chapel Hill for assistance with ICP-MS, confocal microscopy and TEM analyses, respectively. SW would like to acknowledge financial assistance provided by the Amgen Graduate Fellowship.

Keywords

  • Adjuvant
  • Antibody
  • Antigen
  • Cytokine
  • Dendritic cells
  • Green fluorescent protein

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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