Adjuvants have been used as critical components of vaccine.They were used to stabilize the antigens and potentiate the immune responses.Dose sparing is also of interests in recent years to be applied in potential pandemic situations or to lower the costs of vaccines.With the emerging nanotechnology in many aspects including the use in biomedical applications,the application of nanomaterials as vaccine adjuvants also attracted a lot of attentions in recent years.With favorable biological properties,such as well-defined and well-formed nanoparticles,biocompatibility,biodegradability and ability to induce humoral immunity and cellular immunity simultaneously,calcium phosphate nanoparticles (CaP) have the potentials to be developed as an immune potentiator to be used as vaccine adjuvants.Here,we reviewed the basic properties of CaP and their applications as vaccine adjuvants with antigens of different modalities such as inactivated virus,protein and naked DNAs.The mechanism of the adjuvanting effects is briefly described.Further the development of CaP as vaccine adjuvants with some designed surface modification could lead to next generation vaccine adjuvants with improved immune potentiating properties and safety profiles.

OBJECTIVE:To observe clinical efficacy and safety of individual antiviral therapy of tenofovir combined with inter-feron α1b for chronic hepatitis B (CHB). METHODS:96 CHB patients were randomly divided into control group,observation group A and observation group B,with 32 cases in each group. Control group was given entecavir orally,0.5 mg,qd;observation group A was given tenofovir orally,1 piece,qd;observation group B was additionally given interferon α1b,50 μg,3 times a week,on the basis of observation group A. The treatment course lasted for 48 weeks in 3 groups. Clinical efficacy of 3 groups was compared,and the changes of serum liver function indexes,HBV-DNA negative conversion rate and the occurrence of ADR were compared before and after treatment. RESULTS:The total effective rate of observation group B(84.38%)was significantly higher than that of observation group A(62.60%)and control group(37.50%),and that of observation group A was significantly higher than control group,with statistical significance (P<0.05). Compared with before treatment,the serum levels of AST,ALT and TBIL were significantly decreased after treatment in 3 groups;the observation group B were significantly lower than those of obser-vation group A and control group,with statistical significance(P<0.05);there was no statistical significance between observation group A and control group(P>0.05). The negative rate of HBV-DNA in observation group B were significantly higher than those in control group and observation group A after 12 and 24 weeks of treatment,with statistical significance(P<0.05);there was no statistical significance between observation group A and control group (P>0.05). No obvious ADR was found in 3 groups. CON-CLUSIONS:Tenofovir combined with interferon α1b shows significant clinical efficacy for CHB,and is significantly better than that of entecavir and tenofovir alone.

Zika fever is a self-limiting and acute infectious disease caused by Zika virus infection. It is mainly transmitted through the bite of mosquitoes of the Aedes type. It can also be spread through verti-cal transmission. There is evidence that it can also be sexually transmitted from a man to his sex partners due to the presence of the virus in semen. The re-emergence of the virus in 2015 as a major endemic in the South American countries ( which may spread further) warrants better understanding of Zika virus. The outbreaks, transmission routes, virological characteristics and the diagnosis and treatment of Zika virus infection will be summarized in this review. Moreover, the potential correlations between newborn microcephaly and Zika vi-rus infection as well as the possible molecular mechanisms for causing microcephaly such as cell autophagy will also be discussed.

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.

Objective To quantitatively analyze the characteristics of a panel of murine anti-human papillomavirus(HPV)11 L1-derived virus-like particle( VLP ) monoclonal antibodies ( mAbs ) and establish the mAb-based methods for antigen quality analysis.Methods A panel of 22 murine anti-HPV11 mAbs were characterized in details with their isotype, and binding affinity, conformational sensitivity were examined quantitatively in the direct binding ELISA and Western blot.The hemagglutination inhibition activity of mAbs were identified using the hemagglutination inhibition assay and the pseudovirus ( PsV ) neutralization efficiency were examined quantitatively using the PsV-based neutralization assay.The type-specific, highly conformational sensitive and neutralizing mAbs were selected to be used in the sandwich ELISA assay.Results Based on the quantitative and semi-quantitative results, six type-specific, highly conformational sensitive and neutralizing mAbs (2A2, 4A1-3, 16G7, 14A6, 9C1 and 19C7) were identified.These mAbs, along with 10D6 were screened as the capture mAb or as the detection mAb in the sandwich ELISA.Conclusion The binding affinity, conformational sensitivity and neutralization efficiency of anti-HPV11 mAbs were characterized in details.A mAb-based sandwich ELISA assay (14A6:Ag:9C12-HRP) were developed, which could be used in the in vitro potency analysis of HPV11 VLP-based vaccine.

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

OBJECTIVETo investigate the influence of najanalgesin on glutamate-glial transporter 1(GLT-1) in spinal cord of rats after L5 spinal nerve ligation and transection (SNL), and explore the spinal analgesic mechanism of najanalgesin.

METHODOne hundred male SD rats were randomly divided into 6 groups: sham(A), SNL(B), SNL + najanalgesin(C), SNL + saline (D), SNL + najanalgesin + liposome (E), SNL + najanalgesin + liposome + GLT-1 As-ODNs(F) and treated with intrathecal injections of 10 p.L saline (A and D), 40 ng X kg(-1) najanalgesin (C, E and F), qd, respectively. Besides intrathecal administration of najanalgesin the rats were intrathecally injected with 10 microL of GLT-1 antisense oligodeoxynucleotides (As-ODNs) (F) and 10 micdroL of liposome(E) once daily on day 3. The L4-L6 segments of the spinal cord were isolated in 1, 4 and 7 d(A,B,C and D), 7 d(E and F) after surgery. The mRNA and protein of GLT-1 were determined.

RESULTThe SNL model has successfully been set up. Compared to sham group, the expression of GLT-1 mRNA and protein level in group B and D both increased firstly and decreased later, the expression of GLT-1 in group C was significantly increased and kept stable, which were also higher when compared to group D in day 7th. Compared to SNL + najanalgesin group, after intrathecal injection of GLT-1 As-ODNs the GLT-1, expression of GLT-1 in F group significantly decreased. While intrathecal administration of liposome had no significant effect on the spinal GLT-1 expression.

CONCLUSIONNajanalgesin could increase the mRNA and protein expression of GLT-1 in spinal cord, which may be one of its spinal mechanisms of analgesia.

Animals ; Elapid Venoms ; pharmacology ; Elapidae ; Excitatory Amino Acid Transporter 2 ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Male ; Neuralgia ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism

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.

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.