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.

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.

Human coronavirus OC43 (HCoV-OC43) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) belong to the β-coronavirus genus. Since the discovery in 1967, HCoV-OC43 has been continuously circulating in human population and has become one of the common seasonal respiratory viruses. SARS-CoV-2, which has a higher morbidity and fatality rate, appeared at the end of 2019, followed by the emergence of a variety of variants, and the transmission and infection capacity of SARS-CoV-2 has been enhanced. HCoV-OC43 may be similar to SARS-CoV-2 in terms of genomic structure and function, species evolution, epidemic characteristics and clinical manifestations. In this review, the epidemiology, genomics, phylogenetic evolution and other aspects of HCoV-OC43 and SARS-CoV-2 were analyzed. Such an analysis would be helpful to understand the association and differences between the two viruses, and provide reference for understanding the potential threats of HCoV-OC43.

Zinc is one of the essential trace elements for human. It is essential for human health. In recent decades, the distribution and transport of zinc in human body have gradually become more evident. The immunomodulatory effects of zinc on the immune system have also been elucidated. Zinc is involved in regulating the cellular signaling pathways of immune cells and affecting the development of immune organs, the physiological state and function of immune cells and the secretion of cytokines. It is an indispensable element in the immune system and plays an important role in maintaining the integrity and stability of the immune system. This article briefly introduced the distribution and transportation of zinc in the human body, with the emphasis on the relationship between zinc and the development and function of immune cells.

Objective To study the method of dose reconstruction in human body under the photon external radiation accident condition,and to verify the accuracy of the method for the local dose distribution.Methods Based on the open source Monte Carlo tool kit Geant 4 and using the human voxel phantom recommended by ICRP Publication 103,the dose reconstruction method under the condition of external radiation accident was studied to evaluate the average absorbed dose,organ absorbed dose and local dose distribution.To validate the code,several irradiation experiments were implemented in some standard radiation fields by putting TLDs in the tissue equivalent physical phantom ART.A voxel phantom was used to reconstruct the radiation doses,which was created based on the CT scan image of the ART phantom with resolution of 1.57 mm× 1.57 mm× 10.00 mm.The result of experiment were compared with those of dose reconstruction simulation.Results The relative uncertainty of the measured values was 10.9％.The relative uncertainty of the dose reconstruction simulation values was 7.10％ at the non-tissueinterface area and 16.6％ at the tissue-interface area.For 451 measuring points,the average of the simulated value divided by the measured value was 0.972,with the standard deviation of 0.083 8.In the range of 0.95-1.05,0.90-1.10 and 0.80-1.20,and the proportions were 49.2％,79.4％ and 96.4％,respectively.Conclusions The method of Monte Carlo dose reconstruction based on human voxel phantom meets the accuracy requirement of actual uses both at the whole body or organ level and at the local dose distribution level.It can be used as a powerful tool for dose assessment of the exposed people in an external radiation accidents and provide support for diagnosis and treatment.

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.

Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi-domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle management. Specially, the molecular characterization, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parameters and the methods used for obtaining them. The three groups of analytical methods are three essential and integral facets making up the whole analytical package for a mAb-based drug. Such a package is critically important for the licensure and the post-licensure life cycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.
Animals ; Antibodies, Monoclonal ; chemistry ; therapeutic use ; Biological Products ; therapeutic use ; Glycosylation ; Humans ; Kinetics ; Ligands

Objective: This study aims to evaluate the prevention effect and cost-effectiveness of a prophylactic bivalent human papilloma virus (HPV) vaccine. Methods: A multiple health status dynamic model was developed, including natural history of diseases and prevention strategies. We built 19 prevention strategies including visual inspection with acetic acid/lugol's iodine (VIA/VILI) and/or 3 does prophylactic bivalent HPV vaccine administered to adolescent girls at the age of 15 years old every year under the assumption that vaccine coverage and screening coverage were 70%. The incremental cost-effectiveness ratio (ICER), optimal price of 3 does vaccine and cost-effectiveness frontier of these strategies were analyzed compared with no-intervention. The ICER threshold is 152 087 CNY. Results: Compared with no-intervention, Routine vaccination reduced the incidence of cervical cancer by 69.5%, superior to 5 strategies including VIA/VILI screening only. The range of effect was between 9.0% and 69.2%, and the effect of strategy increased significantly with the increase of screening frequency. Combination vaccination with screening at ages of 35 reduced the incidence of cervical cancer by 72.0%, and the effect increased with the increase of screening frequency. Combination vaccination with screening every 3 years between (35-64) years old reduced the incidence by 89.4%. Compared with no-intervention, the ICER of combination vaccination with screening twice between 35 years and 64 years was 121 292 CNY/life-year, which was cost-effective. The price of vaccine had a significant impact on the ICER of the strategy; when the vaccine price was less than 600 CNY, only routine vaccination or supplementary vaccination between 16-39 years old after routine vaccination was cost-effective; when the vaccine price was less than 1 200 CNY, supplementary vaccination between 16-19 years old plus VIA/VILI was cost-effective. Conclusion Ther prevention strategy was cost-effective, which could effectively reduce the incidence of cervical cancer by implementation of HPV vaccination combined with VIA/VILI in suitable aging females.

Cervical carcinoma has brought huge burden on patients, especially in developing countries. Preventive vaccines could effectively reduce the incidence of cervical carcinoma. The high prices were one of the most difficult problem in introducing the vaccine in developing countries, so the cost-effectiveness and health financing of the vaccines should be carefully studied before incorporated into the national immunization program. Thus, researchers used mathematical models to predict the effects of HPV vaccines and to study the cost- effectiveness. In order to understand the current situation on the cost-effectiveness of HPV vaccines in the developing countries, a systematic searching of literature from PubMed, Elsevier Science Direct, Medline, ProQuest, CNKI and Wangfang Data was performed, this study aims to conduct a systematic review from aspects of project source, first author, research areas, research perspectives, prevention strategies, vaccine characteristics, cost-effectiveness.
Cost-Benefit Analysis ; Developing Countries ; Female ; Humans ; Immunization Programs ; Incidence ; Models, Theoretical ; Papillomavirus Infections ; economics ; prevention & control ; Papillomavirus Vaccines ; economics ; Uterine Cervical Neoplasms ; economics ; prevention & control

John Cunningham virus(JCV)is a type of human polyomavirus. It was first isolated from the brain of a patient with progressive multifocal leukoencephalopathy(PML)in 1971 and named after that patient. The seroprevalence of JCV in the general population is 40% to 60% . The mortality rate among patients with AIDS complicated by PML was shown to be 50% . For immunocompromised patients and pa-tients with long-term use of immunosuppressive drugs,JCV would cause fatal polyomavirus associated ne-phropathy(PVAN),viremia and some other related diseases. While the pathogenesis of JCV has well stud-ied,there are no specific prevention and treatment measures for infected individuals. Therefore,reliable, specific and sensitive JCV detection methods in clinical settings are needed. This review describes the pros and cons of different methods for JCV detection with potentials for clinical applications.