| Herpes zoster is a viral infectious skin disease mainly transmitted through the respiratory tract and is highly contagious.The incidence of herpes zoster is increasing at home and abroad,and the posterior neuralgia associated with herpes zoster lasts for months to years.It is difficult for long-lasting antiviral treatment to effectively relieve this pain,seriously affecting patients’ quality of life.Numerous studies have demonstrated that vaccination effectively reduces the incidence of herpes zoster and the incidence and pain of PHN after infection.Live attenuated vaccine(LAV)for herpes zoster,is basically no need to use adjuvant to induce an effective immune response,but there are serious potential safety hazards.However,the VLP vaccine are compatible with traditional aluminium adjuvant,which can significantly enhance the immune effect of the body fluid without affecting the cellular immunity.Based on the issues above,it puts forward in this paper the idea to use protein gE as antigen,and the highly biocompatible polymer PLGA as carrier for nano-particles to carry the immunologic adjuvant in a way of layers.By using the dual immuneenhancing mechanism of nano adjuvant and immunologic adjuvant,and the slowrelease mechanism of nanoparticles,it can enhance humoral immunity that induced by the gE antigen and the effect of cellular immunity.It lays the foundation of developing a safe,efficient and universal herpes zoster recombinant subunit vaccine.The specific research contains the following aspects:(1)Construction and characterization of antigen and herpes zoster nanovaccine The PLAG nanoparticles carring Poly(I:C)by nanoprecipitation technology were used as a composite adjuvant and use it to optimize the preparation parameters to complete the characterization and properties of the nanoparticles;Electrostatic adsorption is adopted to adsorb the gE truncated protein to the surface of the nanoparticles adjuvant and test the gE value in the antigen.(2)In vitro evaluation of Nano-composite adjuvant herpes zoster vaccine To systematically study Nano-composite adjuvant herpes zoster vaccine’s cytotoxicity to DC cells and study the internalization and transport of the vaccine though the cell’s intake of particle and its location.Besides,study the activities situation of the DC cells after getting affected by the vaccine by the way of testing the secretion level and stimulation of the cells.(3)The in vivo immune efficacy of a compound adjuvant herpes zoster nanovaccine.After immunization of C57BL/6 mice with the herpes zoster nanovaccine constructed in the study,the immune effect was evaluated by detecting the level of IgGspecific antibody secretion in the serum of C57BL/6 mice by indirect ELISA,and the immune tendency of the organism was evaluated by the antibody secretion level of IgG 1 and IgG2a.In conclusion,through the synergistic effect of nano adjuvant and adjuvant of Poly(I:C)that with effect of antiviral action and immunoregulation,the effect of gE humoral immunity and cellular immunity is significantly improved and to obtain a new type of herpes zoster nano vaccine that of good security and long-last protective immune effect. |
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