Development And Immunobiological Evaluation Of Nanoparticles Containing An Immunodominant Epitope Of Herpes Simplex Virus

Herpes simplex virus (HSV) 1 and 2 are viruses that infect individuals worldwide and for which there is no cure or vaccine available. The protective response against herpes is mostly mediated by CD8 T lymphocytes that respond to the immunodominant SSIEFARL epitope. However, there are some obstacles concerning the use of free SSIEFARL for vaccine or immunotherapy. The aim of this study was to evaluate the feasibility of nanoencapsulation of SSIEFARL and its immunostimulatory properties. Nano/SSIEFARL was produced by interfacial polymerization in methylmetacrylate, and the physico-chemical properties, morphology and immunobiological parameters were evaluated. To evaluate the ex vivo capacity of Nano/SSIEFARL, we used splenocytes from HSV-1-infected mice to enhance the frequency of SSIEFARL-specific CD8 T lymphocytes. The results indicate that Nano/SSIEFARL has a spherical shape, an average diameter of 352 +/- 22 nm, the PDI was 0.361 +/- 0.009 and is negatively charged (-26.30 +/- 35). The stability at 4 degrees C was 28 days. Also, Nano/SSIEFARL is not toxic for cells at low concentrations in vitro and it is taken up by JAWS II dendritic cells. No histopathological changes were observed in kidneys, liver and lymph nodes of animals treated with Nano/SSIEFARL. Nan/SSIEFARL increased the production of IL-1 beta, TNF-alpha and IL-12 by the dendritic cells. Finally, Nano/SSIEFARL expanded the frequency of SSIEFARL-specific CD8+T lymphocytes at the same rate as free SSIEFARL. In conclusion all data together indicate that SSIEFARL is suitable for nanoencapsulation, and the system produced presents some immunoadjuvant properties that can be used to improve the immune response against herpes.