Preparation and Characterization of Nickel Nanoparticles for Binding to His-tag Proteins and Antigens

Abstract

Ni-NPs can be used to bind strongly to his-tag proteins. This system was demonstrated to have potential applications in vaccine delivery for enhancing immune responses to protein-based vaccines.

Antibody Response to Polyhistidine-Tagged Peptide and Protein Antigens Attached to Liposomes via Lipid-Linked Nitrilotriacetic Acid in Mice

“…(Fig. 6), as reported by Patel and coworkers in the case of p24 attached to wax nanoparticles (35). Omission of MPL from the tris-NTA formulation resulted in a decrease of an order of magnitude in anti-OVA titers (GMT, 1.6 ϫ 10 5 [P ϭ 0.003]).…”

“…6). These findings appear to conflict with the work of Patel and coworkers showing that NTA-Ni(II) wax nanoparticles elicited greater responses to polyhistidine-tagged p24 antigen than control nanoparticles lacking Ni(II) (35). However, this discrepancy may arise from the greater immunostimulatory capacity of the MPL-adjuvanted liposomes than of the nanoparticles used in the study by Patel and coworkers (4).…”

“…Although metal chelation via NTA-Ni(II)-His has been suggested as a site-specific, nondestructive approach to particulate delivery of polyhistidine-tagged antigens (9,35), concerns that the micromolar affinity of monovalent NTA for hexahistidine may be too weak for in vivo applications have arisen (22,27,37,45). We hypothesized that the increased affinity of trivalent NTA for polyhistidine (K D , ϳ1 nM) would translate to increased liposome association and enhanced antibody titers compared to a monovalent NTA linkage (K D , ϳ10 M).…”

“…VOL. 18,2011 NTA LIPOSOME-MEDIATED SUBUNIT ANTIGEN DELIVERY 295 formulation lacking Ni(II) in which antigen was unassociated (35). In contrast, when Chikh and coworkers attached a short decahistidine-tagged peptide containing a cytotoxic T lymphocyte epitope to mono-NTA liposomes, they did not observe significantly increased peptide-specific splenocyte interferon gamma secretion compared to that obtained with a formulation lacking NTA following immunization of mice (9).…”

“…This is of particular importance for delivery of membrane protein antigens such as HIV-1 gp41 and other viral envelope glycoproteins, where presentation of key neutralizing determinants in their native orientation within a membrane context is desired (31). A recent study reported the use of lipid-anchored NTA for attachment of polyhistidine-tagged HIV-1 Gag p24 antigen to wax nanoparticles (35). These formulations elicited superior antip24 antibody and T lymphocyte responses compared to p24 admixed with nanoparticles lacking Ni(II) or to p24 adsorbed onto alum.…”