[Development of vaccine adjuvants using polymeric nanoparticles and their potential applications for anti-HIV...

The development of a prophylactic/therapeutic HIV-1 vaccine based on recombinant proteins is needed for the control of the worldwide AIDS epidemic. Subunit protein and peptide vaccines are generally very safe, with well-defined components. However, these antigens are often poorly immunogenic, and thus require the use of adjuvants to induce adequate immunity. Particulate adjuvants (e.g. micro/nanoparticles, emulsions, ISCOMS, liposomes, virosomes, and virus-like particles) have been widely investigated as HIV-1 vaccine delivery systems. Antigen uptake by antigen-presenting cells (APC) is enhanced by the association of the antigens with polymeric micro/nanoparticles. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into APC. More importantly, particulate antigens have been shown to be more efficient than soluble antigens for the induction of immune responses. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanospheres composed of hydrophobic polystyrene and hydrophilic macromonomers. Core-corona type polymeric nanospheres have applications in various technological and biomedical fields, because their chemical structures and particle size can be easily controlled. In this study, we focused on the development of a HIV-1 vaccine using polymeric nanoparticles. We evaluated the immunization strategies for HIV-1-capturing core-corona type polystyrene nanospheres that would efficiently induce HIV-1-specific IgA responses in female mice and the macaque genital tract. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of poly (gamma-glutamic acid) (gamma-PGA) for protein-based vaccine delivery. These HIV-1-capturing nanospheres and protein-loaded gamma-PGA nanoparticles have shown unique potential as vaccine carriers.