Engineering blend particle delivery platform for subunit vaccines against mucosally transmitted viral infections
The key aspect of a vaccine delivery platform is to be easily programmed towards different antigens and adjuvants application. Antigens or adjuvants that are derived from various pathogens are diverse in a number of physical chemical properties, such as size, charge, and solubility. A polymer nanoparticle system made of the mixture of pH-insensitive polymer, such as poly(lactic-co-glycolic acid) (PLGA) and pH-sensitive polymer has been developed in our lab for vaccine delivery. By modulating the ratio of pH-responsive copolymers, we were able to control both intracellular and extracellular release of protein antigens with different charge properties. Co-delivering the mixture of optimized antigen and adjuvants particles to mice subcutaneously, the quantity and quality of both primary and memory immunity were successfully improved compared to the positive control which contained antigen mixed with aluminum hydroxide (Alum) adjuvant. Unlike Alum, which induced Th2-dominant humoral responses, blend particles elicited robust Th1-dominant responses. Additionally, the quality of cellular responses was improved by blend particle systems. Higher level of polyfunctional CD4+ T cells was induced by particles compared to Alum control. In combination of a novel mucosal vaccination strategy, this particle system was tested to protect mice from genital Herpes Simplex Virus-2 (HSV-2) infection. More than 500 millions of people are estimated to be infected with HSV-2 worldwide and HSV-2 seropositive persons have a 2 to 4 fold increased risk of acquiring HIV-1 infection. Lacking sufficient immunity, candidate HSV-2 vaccines that were protective in animal model, however, have not been successful in human clinical studies in decades. Our results showed that our strategy recruited sufficient immunity in local tissue and has efficiently protected the mice against HSV-2 infection. This pH-responsive blend particle system represents a simple and promising delivery platform for subunit vaccine development against viral infections.
- Chemical engineering