Binding, Internalization, and Antigen Presentation of Vaccine-Loaded Nanoengineered Capsules in Blood

Standard vaccine technologies based on the induction of antibodies are ineffective in preventing many globally important infectious diseases, including HIV/AIDS. T cell immunity correlates with the control of many chronic infectious diseases, including HIV in humans and SIV in monkeys. However, inducing persistent T cell immunity has proven difficult, in part due to problems with prolonged availability of safe antigens to specialized APCs such as dendritic cells (DCs). Recent adenovirus vector-based strategies used to induce T cell immunity have actually heightened susceptibility to HIV-1 infection, emphasizing the need for novel, safer, and more effective means to induce immunity. Peptides are safe vaccine antigens, however proteases in vivo can rapidly degrade peptide-based vaccines and this has limited their utility to date. Our group recently showed that mixing free peptides with macaque monkey blood cells effectively stimulates T cell immunity and prevents AIDS in SIV-infected monkeys. However, this technology is limited by the need for high doses of peptides and ex vivo mixing of the peptides with blood APCs to prevent rapid degradation of the vaccine antigens. Other effective methods, such as targeting labile vaccine antigens to purified cultured DCs necessitate extensive ex vivo isolation of DCs, are also impractical for widespread use. Novel technologies to protect peptide antigens for delivery to APCs in vivo are required in order to improve HIV vaccine strategies using safe immunostimulatory peptides.