Virus-Like Particle, Liposome, and Polymeric Particle-Based Vaccines against HIV-1

Abstract

It is acknowledged that vaccines remain the best hope for eliminating the HIV-1 epidemic. However, the failure to produce effective vaccine immunogens and the inability of conventional delivery strategies to elicit the desired immune responses remains a central theme and has ultimately led to a significant roadblock in HIV vaccine development. Consequently, significant efforts have been applied to generate novel vaccine antigens and delivery agents, which mimic viral structures for optimal immune induction. Here, we review the latest developments that have occurred in the nanoparticle vaccine field, with special emphasis on strategies that are being utilized to attain highly immunogenic, systemic, and mucosal anti-HIV humoral and cellular immune responses. This includes the design of novel immunogens, the central role of antigen-presenting cells, delivery routes, and biodistribution of nanoparticles to lymph nodes. In particular, we will focus on virus-like-particle formulations and their preclinical uses within the HIV prophylactic vaccine setting.

Adjuvant Potential of Poly-α- l -Glutamine from the Cell Wall of Mycobacterium tuberculosis

“…Additionally, due to its particulate nature, PLG may slow down or resist proteolytic cleavage in the eukaryotic proteasome (44) and exert a "depot effect" by increasing residence time at the site of vaccination, thereby promoting activation of the APCs and phagocytosis. A similar mechanism of action has been reported for synthetic poly(lactic-coglycolic acid) (PLGA) particles (45), virus-like particle (VLP)-based vaccines (46,47), and the immune-stimulating complexes (ISCOMS) (48). Presently, sustained efforts are needed to reduce the dosage of PLG for optimum action.…”

Nanomedicine review: clinical developments in liposomal applications

“…Liposomes are bilayer spherical vesicles composed by phospholipids and cholesterol that in water create at least one lipid bilayer surrounding an aqueous core, which may encapsulate both hydrophilic drugs (e.g., Doxil ® , encapsulated doxorubicin in the aqueous core) and hydrophobic compounds (e.g., AmBisome ® , trapped amphotericin B) immersed in the lamellae by Van der Waals forces (Senapati et al 2018;Gonda et al 2019;Gao et al 2018), see Fig. 2.…”

“…Liposomes have a diameter ranging from 20 nm to more than several hundred micrometers, as shown in Table 2. Particle size affects their pharmacokinetics, tissue extravasation, tissue diffusion, hepatic uptake, kidney excretion, and clearance rate from the site of injection (Zamani et al 2018;Gao et al 2018;Olusanya et al 2018;Kraft et al 2014). Only liposomes of a mean diameter between 100 and 150 nm are able to enter fenestrated vessels in the liver endothelium, secondary lymphoid structures, or tumor microenvironments (Bourquin et al 2018;Gao et al 2018;Kraft et al 2014).…”

Strategies for inducing effective neutralizing antibody responses against HIV-1

“…The physicochemical properties of nanoparticles, such as shape, size and surface chemistry, can affect their effectivity (reviewed in [181]), thus representing important features to be fine-tuned. A number nanoparticle platforms have been used for displaying Env antigens [188,189]. VLPs based on the HIV-1 virion carry native Env spikes, but the intrinsic low density of spikes on the surface of HIV-1 virions negates some of the important immunological benefits of nanoparticle presentation.…”