Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

Original Research

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Authors: Weili Yan, Anekant Jain, Ronan O’Carra,  Jerold G Woodward, et al.

Published Date July 2009 Volume 2009:1(Default) Pages 1 - 11

DOI: http://dx.doi.org/10.2147/HIV.S5729

Weili Yan¹, Anekant Jain¹, Ronan O’Carra²,  Jerold G Woodward³,  Wenxue Li⁴, Guanhan Li⁴, Avindra Nath⁴,  Russell J Mumper¹

¹Division of Molecular Pharmaceutics and the Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; ²Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky; ³Department of Microbiology, Immunology and Molecular Genetics,  University of Kentucky, Lexington, KY, USA; ⁴Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

Abstract: Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the human immunodeficiency virus (HIV) his-tagged Tat (his-Tat) protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by subcutaneous injection with his-Tat/Ni-NP formulation (1.5 µg his-Tat/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific immunoglobulin G titer with his-Tat/Ni-NPs was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP-immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery.

Keywords: nanoparticle, nickel, HIV, antigen co-delivery, vaccine