1.Activities of polysaccharides in combination with aluminum adjuvant in varicella-zoster subunit vaccines
Meifeng NIE ; Yike LI ; Xiaofen HUANG ; Tong CHENG ; Qinjian ZHAO
Chinese Journal of Microbiology and Immunology 2019;39(6):454-459
Objective To evaluate the immunostimulatory effects of polysaccharides, including Lycium barbarum polysaccharides ( LBP) , Angelica polysaccharides ( AP) , Licorice polysaccharides ( LP) and Inulin polysaccharides ( IP) , used alone or in combination with aluminum adjuvant on the recombinant protein of varicella-zoster virus (VZV) glycoprotein (gE) as an immunogen in mice. Methods BALB/c mice were randomly divided into 11 groups with five in each group. Intramuscular injection was given at Days 0 and 14. Serum samples were collected at weeks 0, 2, 3, 4 and detected for total anti-gE IgG titers and an-tibody subtypes by indirect ELISA. The mice were sacrificed at week 4 to collect spleen lymphocytes aseptic-ally. CCK-8 method was used to evaluate the proliferation of spleen lymphocytes. The levels of IFN-γ and IL-4 were measured by ELISA. The percentages of CD3+CD4+ and CD3+CD8+ T cell subsets were deter-mined by flow cytometry. Results The four plant-derived polysaccharides in combination with aluminum adjuvant showed good adjuvant activities. LP combined with aluminum adjuvant effectively increased the titer of IgG2, promote the proliferation of splenocytes and enhanced the secretion of IFN-γ and IL-4. Further-more, it also induced CD3+CD4+ and CD3+CD8+ T cell proliferation in vivo. Conclusions The four plant-derived polysaccharides in combination with aluminum adjuvant could all enhance antibody production. LP combined with aluminum adjuvant could induce cell-mediated immune responses, suggesting that it might be a promising adjuvant for varicella-zoster subunit vaccines.
2.Capsid destabilization and epitope alterations of human papillomavirus 18 in the presence of thimerosal
Huang XIAOFEN ; Li YIKE ; Nie MEIFENG ; Yue MINGXI ; Li YUFANG ; Lin ZHIJIE ; Pan HUIRONG ; Fang MUJIN ; Wu TING ; Li SHAOWEI ; Zhang JUN ; Xia NINGSHAO ; Zhao QINJIAN
Journal of Pharmaceutical Analysis 2021;11(5):617-627
Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.
3.Progress in therapeutic monoclonal antibodies targeting hepatitis B surface antigen
Mingxi YUE ; Meifeng NIE ; Xiaofen HUANG ; Tianying ZHANG ; Qinjian ZHAO
Chinese Journal of Microbiology and Immunology 2021;41(10):805-810
Chronic hepatitis B (CHB) is often treated with drugs such as interferons and nucleoside (acid)/nucleotide (acid) analogs. While these drugs are effective in controlling the viral loads, they are not able to eliminate hepatitis B virus (HBV) from the body completely. Besides, side effects and drug resistance may by caused by the long-term use of these drugs. Several monoclonal antibodies (McAbs) against HBV, mostly against hepatitis B surface antigen (HBsAg), have been demonstrated with viral neutralization capability and with effective inhibition of HBV replication in relevant animal models. The use of a McAb individually or in combination with another therapy has the potentials to achieve functional cure of CHB. In this review, we summarized the encouraging results from the research and development of anti-HBV McAbs in clinical or pre-clinical development stage, aiming to provide new idea for the treatment of CHB.