E. Bayon, J. Morlieras, L. Gosse, A. Gonon, N. Bosquet, R. Le Grand, P.N. Marche, F.P. Navarro
Keywords: adjuvant delivery systems, vaccines, HIV, nanostructured lipid carriers
Summary:Fighting HIV pandemic is one of today’s major health priorities and vaccination remains the most challenging issue against HIV propagation. Until now, the best vaccine candidate showed only 30% protection in RV144 clinical trial . Therefore, vaccine efficacy must be improved while maintaining a good safety profile. For this purpose, synthetic particulate systems, especially Nanostructured Lipid Carriers (NLC) are of high interest for delivering protein antigens to Antigen Presenting Cells (APC). One promising approach to promote vaccine potency is to trigger robust cell-mediated immune responses. Interestingly, cellular immunity directed to HIV-1 p24 capsid antigen has been reported to be associated with a diminution of viral load . Here, we report the use of NLC, previously described as an efficient antigen carrier , for the vectorization of p24 antigen together with CpG immunostimulant in the aim to induce potent cell-mediated immune responses. P24 antigen was chemically grafted to the surface of NLC. In addition, we took advantage of NLC versatility by designing a cationic particle (NLC+) for carrying CpG immunostimulant by electrostatic interaction. Immunization studies in mice showed that p24 transported by NLC highly enhanced the production of antibodies, while NLC+ carrying CpG was required for the induction of cell-mediated responses. Indeed, NLC+ efficiently transported CpG inside APC, leading to their efficient activation. Both CD4 and CD8 T lymphocytes were activated, as demonstrated by their secretion of IFNγ upon stimulation with antigen. P24 and CpG vaccine formulations were further evaluated through an immunization study on non-human primates. They received 4 vaccine doses and their immune markers were followed every 2 weeks during 30 weeks. Antibody production and T cell activity reached high levels and persisted for weeks. These results highlight the benefit from using NLC to deliver p24 antigen and CpG immunostimulant in the aim of inducing sustained humoral and cell-mediated immune responses required for controlling HIV. Future experiments will include protective studies through viral challenges, thus paving the way toward the design of innovative HIV vaccines based on non viral vectors.