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

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. Optimizing HIV p24 vaccine responses To date, HIV vaccines have resulted in poor or absent protection. A team led by Fabrice P. Navarro at the CEA LETI use the conserved HIV capsid protein p24 vectorized into cationic nanostructured lipid carriers (NLC-p24) along with NLC-delivered CpG. Owing to their small size, NLCs gain access to lymph nodes and deliver antigen directly to antigen presenting cells. Anti-p24 responses have been associated with effective HIV control, making them an attractive vaccine antigen, but they are poorly immunogenic. NLC-p24 shows a good safety profile while at the same time being able to elicit robust humoral and cellular immune responses in both mice and Cynomolgus macaques. NLC-mediated delivery of both p24 and CpG results in more effective immune stimulation than delivery of free antigen and adjuvant. These findings demonstrate the possibility of priming effective responses to a potent but otherwise poorly immunogenic HIV antigen.