Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative nanostructured lipid carriers as delivery systems: evidences in mice and non-human primates

Abstract

HIV is one of the deadliest pandemics of modern times, having already caused 35 million deaths around the world. Despite the huge efforts spent to develop treatments, the virus cannot yet be eradicated and continues to infect new people. Spread of the virus remains uncontrolled, thus exposing the worldwide population to HIV danger, due to the lack of efficient vaccines. The latest clinical trials describe the challenges associated with developing an effective prophylactic HIV vaccine. These immunological obstacles will only be overcome by smart and innovative solutions applied to the design of vaccine formulations. Here, we describe the use of nanostructured lipid carriers (NLC) for the delivery of p24 protein as a model HIV antigen, with the aim of increasing its immunogenicity. We have designed vaccine formulations comprising NLC grafted with p24 antigen, together with cationic NLC optimized for the delivery of immunostimulant CpG. This tailored system significantly enhanced immune responses against p24, in terms of specific antibody production and T-cell activation in mice. More importantly, the capacity of NLC to induce specific immune responses against this troublesome HIV antigen was further supported by a 7-month study on non-human primates (NHP). This work paves the way toward the development of a future HIV vaccine, which will also require the use of envelope antigens.

Development and validation of a novel UPLC-ELSD method for the assessment of lipid composition of nanomedicine formulation

“…In addition, particle size and viscosity of the core can be tuned, resulting in high payloads, controlled drug release and improved drug bioavailability to appropriate biological sites [13]. More recently, our lipid nanocarriers showed great potential as innovative delivery systems of protein antigens by chemical modification of the shell [14,15]. Far more complex than liposomes, our lipid nanocarriers are composed of a lipid core comprising a mixture of saturated and unsaturated glycerides, and a surfactant shell comprising a mixture of PEGylated surfactants and phospholipids.…”

Advancements in prophylactic and therapeutic nanovaccines

“…Bayon et al, have also shown the capacity of nano-lipid complexes (NLC) to induce p24 specific immune responses against HIV in non-human primates (NHP). Four intradermal immunization over a period of 7 months showed that NLC-loaded p-24 antigen elicited significantly higher p24-specific antibodies as compared to the combination of free p24 antigen and CpG adjuvant [166] .…”

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

“…The use of 4DV3 as the targeting ligand resulted in enhanced endocytosis due to the uptake of 4DV3 functionalized nanocarriers combined with the allosteric interaction with CXCR4, suggesting that 4DV3 peptide could be considered as a dual function ligand. Bayon et al (2018) developed vaccine formulations comprising nanostructured lipid carriers (NLC) grafted with p24 antigen, together with cationic NLC optimized for the delivery of immunostimulant CpG, which was able notably enhance immune responses against p24 manifested in specific antibody production and T cell activation in mice as well as in nonhuman primates.…”