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Objective(s): In the current work, poly D, L lactide-co-glycolide (PLGA) particles were applied for a viral vaccine for the delivery of antigens in cytosolic pathway by increasing the antigen presentation to T-lymphocytes. HPV-E7 protein with PLGA particles has been reported as a potent adjuvant for HPV vaccine by encapsulating protein into the PLGA particles. Polysaccharide from Pleurotus sajor-caju was also applied as a potent immunomodulator. Materials and Methods: HPV-E7 protein and Pleurotus sajor-caju polysaccharides (PSC) were encapsulated into PLGA nanoparticles. This combination comprised a strategy to induce helper and cytotoxic T-lymphocytes (CTL) expansion.  Mice antibodies and T-lymphocyte expansion were investigated in comparison between encapsulated E7 protein into PLGA nanoparticles (E7PLGA) and E7 protein with PSC encapsulated into PLGA nanoparticles (PSC-E7PLGA). Results: The results showed that E7PLGA and PSC-E7PLGA could induce antibody response to HPV. The PSC-E7PLGA could increase the level of viral antigen-specific IgG antibodies. The cellular immune responses are also significantly enhanced by expansion of helper T-lymphocytes and CTL. PSC-E7PLGA was shown to be significantly higher in immunomodulating activity than E7PLGA. Conclusion: Thus, the encapsulation of polysaccharide and HPV-E7 antigen into PLGA nanoparticles is a strategy for development of HPV vaccine.