Phospholipid Bilayer-Coated Aluminum Nanoparticles as an Effective Vaccine Adjuvant-Delivery System

Abstract

The phospholipid bilayer-coated aluminum nanoparticles (PLANs), formed via chemisorption, were prepared by reverse ethanol injection-lyophilization (REIL) utilizing the phosphophilicity of aluminum. The anhydrous antigen-loaded PLANs obtained by REIL proved stable, satisfying using the controlled-temperature-chain instead of the integrated cold-chain for distribution, and could be rehydrated to reconstitute instantly an aqueous suspension of the antigen-PLANs, which were more readily taken up by antigen-presenting cells and, when given subcutaneously to mice, induced more robust antigen-specific humoral and cellular immunoresponses but less local inflammation than the antigen-alum. Thus, the PLANs are a useful vaccine adjuvant-delivery system with advantages over the widely used naked alum.

Liposomes Used as a Vaccine Adjuvant-Delivery System

“…To date, various types of liposomes have been developed for delivery of drugs or vaccines, including unilamellar vesicles, multilamellar vesicles (MLVs), multivesicular liposomes (MVLs) (Figure 2) and the liposomes with special structural features, such as cochleates [25,30], bilosomes [31], niosomes [32], the inorganic nanoparticle-cored liposomes such as phospholipid bilayer-coated aluminum nanoparticles (PLANs) [28], and the interbilayer-crosslinked multilamellar vesicles (ICMVs) [33]. Unilamellar liposomes are a spherical chamber/vesicle, bounded by a single bilayer of an amphiphilic lipid or a mixture of such lipids, containing aqueous solution inside the chamber.…”

“…, BioTek Instruments, Inc., Vermont, USA) [25,28]. There are five types of ELISA, including indirect ELISA, direct ELISA, sandwich ELISA, competitive ELISA and ELISPOT, and only a few differences exist amid these ELISA protocols, with the main ELISA principle and lots of procedures being the same.…”

“…For example, recently, multifunctional liposomes have been successfully constructed being anchored with a toll-like receptor (TLR) ligands, including lipid A for TLR4, CpG-ODN for TLR9, and the synthetic molecules with a distal of mannose group for the C-type receptors on APCs, such as dendritic cells (DCs), macrophages (MPs), and even been fabricated into microneedles for penetration of skin and mucosa to further enhance delivery efficiency [24]. These kinds of multifunctional liposomes as a VADS proved highly effective in both targeting delivery of vaccine to APCs and enhancing antigen presentation of APCs to T-cells fulfilling a dual function of delivery and adjuvancy for vaccines [11,24,25,27,28].…”

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

“…[34][35][36] The isolated antigenic proteins, used for constituting so called subunit vaccines, are often entrapped or integrated into the functional particles such as liposomes, PLGA particles, virus like particles (VLPs), which may be combined with biofunctional materials including adjuvants to increase the delivery and immunization efficiency of vaccines. 35,37 The whole live attenuated or inactivated pathogens can rarely be entrapped in micro/nanoparticles due to their large individual size and therefore are usually directly incorporated in or coated on the surface of MA microneedles and, also, may be separately delivered under the assistance by poking with independent MAs. However, MA delivery of vaccines composed of the nonvirulent whole pathogens, which, though, are actually the micro/nano-sized particles, has, whether or not, been widely tested or validated in the clinic and is not yet included in this paper which focuses on only the artificial micro/nanoparticles.…”

Aluminum (Oxy)Hydroxide Nanosticks Synthesized in Bicontinuous Reverse Microemulsion Have Potent Vaccine Adjuvant Activity

“…14–16 Such size-dependent enhancement of the adjuvant effect of aluminum salt-based materials has also been reported by others. 4, 17 For example, Wang and colleagues developed lipid-enveloped aluminum hydroxide nanoparticles with stronger adjuvant activity than aluminum hydroxide microparticles. 17 In addition to the particle size, other properties of aluminum salt-based materials can influence their adjuvant activity as well.…”