Immunological Study Of Herpes Zoster Subunit Vaccine Combined With Different Adjuvants

Herpes zoster（HZ）is a disease with high incidence in aged and immunocompromised populations,caused by reactivation of varicella-zoster virus（VZV）,and is often accompanied by severe complications.The live attenuated vaccine Zostavax^?was the first prophylactic vaccine approved for marketing,while the recombinant subunit vaccine Shingrix^?using AS01 as adjuvant showed higher protective efficacy than the live attenuated vaccine.In this study,we designed a series of adjuvanted herpes zoster subunit vaccines based on our adjuvant platform,and evaluated and compared their performances in mice to obtain candidate recombinant herpes zoster subunit vaccine with promising clinical application.In this study,using glycoprotein E as antigen and C57BL/6 mice pre-immunized with live attenuated vaccine as model,herpes zoster subunit vaccine combined with different adjuvants were injected intramuscularly to mice and their safety and performance were investigated and compared.In addition,the long-lasting performance of varied adjuvanted vaccines was also evaluated.As for adjuvant,two nano-emulsion adjuvants of MF59 and AS03,and two immunostimulants of Cp G and QS-21 were selected and combined.Mice were immunized with either emulsion alone or emulsion plus one immunostimulant.The safety of vaccines was evaluated in terms of body weight and body temperature of mice after inoculation,while the immune response was investigated in terms of serum g E-specific binding antibody titer,antibody subtype,spleen cell cytokine secretion,g E-specific IFN-γ⁺T cell through ELISpot,and multifunctional T cell frequency with flow cytometry.The results indicated that MF59and AS03 showed comparable efficiency in inducing g E-specific antibody.However,the addition of Cp G led decreased antibody production to varied extents,while combining with QS-21 greatly improved humoral immune response induced by the emulsion.In case of cellular immunity,mice immunized with MF59 combined with QS-21 adjuvant showed a higher number of IFN-γ⁺T cells and a higher frequency of multifunctional T cells.In case of long-lasting immune response,combining MF59 with QS-21 also showed superior performance over other combinations.In summary,g E protein combined with MF59+QS-21 can not only enhance antigen-specific humoral and cellular immunity,but also induced a long-lasting immune response after two-dose inoculations in C57BL/6 mice pre-immunized with live attenuated vaccine.The above adjuvant combination is a promising candidate among all evaluated ones in this study.Further study is needed to illustrate its performance in aged mice.This study paved way to the research and development of novel recombinant herpes zoster subunit vaccine.