Engineering the quality and quantity of adaptive immunity against mucosally transmitted viral infections by using blend particle system

X. Zhan, H. Shen
University of Washington, US

Keywords: pH-sensitive polymer particle, vaccine delivery, adaptive immunity, mucosal virus infection

Summary:

Our laboratory has developed a nanoparticle system made of the mixture of pH-insensitive polymer, poly(lactic-co-glycolic acid) (PLGA), and pH-sensitive polymers for vaccine delivery. The key aspect of a vaccine delivery platform is that it can be easily programmed towards diverse antigens and adjuvants. We investigated how to control both intracellular and extracellular release of protein antigens with different charge properties and adjuvants by tuning the ratio of pH-responsive copolymers. Co-delivery of the optimized antigen and adjuvants particles successfully improved the quantity and quality of both primary and memory immunity compared to the mice immunized by antigen mixed with aluminum hydroxide (Alum) adjuvant. Blend particles elicited robust Th1-dominant responses and higher level of polyfunctional CD4+ T cells compared to Alum control. We also observed that the quality and quantity of immunity enable to be modulated by the loading of antigens. 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. Our results suggested that the quality and quantity of T cell immunity play important roles for the protection against HSV-2. This pH-responsive blend particle system represents a promising delivery platform for vaccine development against viral infections.