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

Emilie Bayon,Fabrice P Navarro,Thomas Courant,Roger Le Grand,Alexis Gonon,Leslie Gosse,Jessica Morlieras,Nathalie Dereuddre-Bosquet,Patrice N Marche

doi:10.1038/s41541-018-0086-0

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.

Highlights

Fighting the HIV pandemic is one of the major priorities for healthcare worldwide
We recently described the delivery of protein antigens to dendritic cells (DC) for efficient antigen presentation to T cells using nanostructured lipid carriers (NLC)
Gag p24 antigen was selected as a well-characterized HIV-1 capsid protein antigen which has been widely used in immunological studies involving non-human primates (NHP).[22,23,24,25,26,27,28,29]

Summary

Introduction

According to UNAIDS statistics from 2016, HIV has already caused 35 million deaths around the world, with 76 million people having been infected since the beginning of the epidemic in the 1970s. Despite many prevention campaigns and the availability of medical devices, every year since 2010, around 2 million new infected cases have been counted.[1] Progress in drug development produced highly active antiretroviral therapy (HAART), which has considerably improved life expectancy and quality of life for HIVcarriers.[2] today, HAARTs alone are insufficient to control the epidemic because they fail to effectively eradicate the virus in treated individuals[3] and they are only available to a limited number of patients.[1] Today, all the epidemiological models predict that to efficiently control the spread of HIV would require efficient prophylactic strategies, like vaccines

Objectives

Methods

Results

Conclusion