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Objective:To retrospectively analyze the prevalence and genotype distribution of human papillomavirus (HPV) among women in mainland China from the introduction of cervical cancer vaccine to its marketing in China, so as to provide data for comparing HPV prevalence after the application and gradual promotion of HPV vaccine.Methods:Related articles published during 2006 to 2016 were retrieved from PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases. Data about HPV infection in women receiving physical examination or routine cervical cancer screening and female outpatients were collected and analyzed.Result:A total of 270 articles were retrieved, in which the sampled women were aged from 13 to 90 years old. Seventy-two articles were about HPV infection in women screened for cervical cancer with a sample size of 580 308 people. The overall results showed that during the 11 years, the five most common high-risk HPV genotypes were HPV52, 16, 58, 68 and 18, and the common low-risk HPV genotypes were HPV81, 43 and 6. The distribution of HPV genotypes varied in different regions, but HPV16, 52 and 58 were always the predominant genotypes. Among the 270 collected articles, 200 analyzed HPV infection in female outpatients with a total of 675 035 cases. The results showed that the top five high-risk HPV genotypes with high prevalence were HPV16, 52, 58, 18 and 33, and the common low-risk types were HPV6, 11 and 81. The analysis of HPV infection rate in seven geographical regions indicated that, although the distribution of the commonly circulating high-risk HPV genotypes varied in different regions, HPV16, 52 and 58 remained the predominant genotypes.Conclusions:The present study showed that the prevalence and genotype distribution of HPV infection varied by region, but HPV16, 52 and 58 were always the most common high-risk genotypes and HPV6 was the predominant low-risk genotype in both women screened for cervical cancer and female outpatients. Besides that, the infections of other high-risk genotypes, such as HPV53 and 68, should also be of concern.
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Objective To investigate the physicochemical properties and immunogenicity of virus like particles(VLPs) in two different conformations assembled from the essential capsid protein VP1 of GⅡ.4 norovirus(NoV) in Hansenula polymorpha. Methods NoV GⅡ.4 VLPs in two different conforma-tions were prepared from high-density fermentation of recombinant engineered strains and VLPs purification. Physicochemical properties of the two forms of VLPs were identified by Western blot,size-exclusion high per-formance liquid chromatography (SEC-HPLC), dynamic light scattering(DLS) and transmission electron microscopy. Serum VLPs binding activities and blocking activities against VLPs binding to histo-blood group antigen(HBGA-VLPs) were evaluated after immunization of BALB/c mice with the two forms of VLPs. Re-sults VLPs of two different diameters with high homogeneity were obtained after purification. DLS results showed that particle sizes of two VLPs were 53.98 nm and 45.18 nm,respectively. The two VLPs were sim-ilar in binding abilities to HBGA receptors. Serum VLPs binding activities and blocking activities against HBGA-VLPs were found higher in NoV-VLP-L than NoV-VLP-S,but the difference was not statistically sig-nificant (P>0.05). Conclusion VLPs in two different conformations were obtained by expressing NoV GⅡ.4 VP1 proteins in Hansenula polymorpha. Though they were similar in physicochemical properties and immunogenicity,the NoV-VLP-L might be potential antigen candidates for the development of recombinant human norovirus vaccine.
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Objective To evaluate the immunopotentiating effect of cyclic guanosine monophos-phate-adenosine monophosphate (cGAMP) as an adjuvant on norovirus (GⅡ. 4) virus like particles (VLPs) in the development of norovirus vaccine. Methods BALB/c mice were intramuscularly immunized with norovirus (GⅡ.4) VLPs composed of capsid protein VP1 in combination with cGAMP or Al(OH)3. Norovirus VLPs-specific antibodies in serum were detected by ELISA. A synthetic histo-blood group antigen (HBGA)-VLPs blocking assay was used to analyze neutralizing antibodies against norovirus VLPs in serum samples. Results Immunization with norovirus VLPs in the presence of cGAMP induced a strong humoral immune response in BALB/c mice. Levels of specific IgG antibodies in serum induced by using cGAMP as the adjuvant were significantly higher than those induced by using Al(OH)3adjuvant when immunization of BALB/c mice with the same dosage of VLPs. The antibody level induced by 1 μg of VLPs in combination with cGAMP was equivalent to that elicited by 10 μg of VLPs combined with Al(OH)3adjuvant. Results of the synthetic HBGA-VLPs blocking assay showed that the blocking rate in cGAMP+VLPs immunization group were significantly higher than that in Al(OH)3+VLPs immunization group when using the same dosage of VLPs. No significant difference in blocking rate was observed between cGAMP+VLPs(1 μg) and Al(OH)3+VLPs (10 μg) immunization groups. Conclusion cGAMP significantly enhanced the specific humoral immune response induced by norovirus (GⅡ.4) VLPs in mice as compared with Al(OH)3adjuvant. It might be used as a novel adjuvant to replace the traditional aluminum adjuvant in the development of norovir-us vaccine.
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Objective To evaluate the immune effects of virus-like particles ( VLPs) of VP1 pro-teins derived from norovirus GⅠ. 1 and GⅡ. 4 genotypes expressed in Hansenula polymorpha expression sys-tem. Methods SDS-PAGE and Western blot assay were performed to detect the purity of GⅠ. 1 and GⅡ. 4 VP1 proteins after purification. Morphologies of the recombinant VLPs were observed under transmission electron microscopy ( TEM) . Sizes and distributions of the VLPs were analyzed by dynamic light scattering analyzer. BT50(50% of blocking titer) was detected by HBGA (histo-blood group antigen) blocking assay in BALB/c mice immunized with different regimens. Results SDS-PAGE analysis of the purified recombinant GⅠ. 1 and GⅡ. 4 VP1 proteins showed that their purity were greater than 90%. Western blot assay con-firmed the specific bands of VLPs. TEM images showed that the sizes of purified GⅠ. 1 and GⅡ. 4 VP1 VLPs were at a mean diameter of 30-50 nm with clear border and high homogeneity, which was similar to that of wild virus. BT50 significantly increased in the groups, in which Al( OH) 3 was used as adjuvant. Con-clusion Animal studies have shown that administration of GⅠ. 1 and GⅡ. 4 VP1 VLPs in the presence of Al( OH) 3 induces detectable HBGA-blocking antibody, indicating that GⅠ. 1 and GⅡ. 4 VP1 VLPs are promising candidates for norovirus vaccine.
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Objective To analyze the genotype distribution of human papillomavirus( HPV) strains and their epidemiological characteristics in cervixes of Chinese females. Methods Pertinent litera-tures published during 2004 to 2013 were screened from PubMed,China National Knowledge Infrastructure (CNKI)and Wanfang database for data analysis. Results There were 245 studies screened out for the me-ta-analysis. A total of 661 658 cases met the inclusion criteria,ranging from 16 to 87 years old. All prov-inces and territories of China were covered by the data. The overall rate of HPV infection in cervix was 25. 0% among Chinese females. The predominant high risk genotype of human papillomavirus strains was HPV16,followed by HPV52,HPV58,HPV18,HPV33 and HPV31. HPV52 and HPV58 genotypes were more prevalent than HPV18 genotype. HPV35 and HPV45 genotypes were less popular. Conclusion The study suggested that the HPV infection showed obvious regional differences in genotypes. The genotype dis-tribution of HPV infection in China was different from that in other regions of the world. There were differ-ences with genotype distribution of HPV strains among seven geographic regions of China.
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Objective To evaluate the immunogenicity of group A and C meningococcal polysaccharides conjugates using different proteins as carriers. Methods Heat-labile enterotoxin B subunit (LTB)pentamer form was expressed in E. coli. The target protein was identified and purified by cation-exchange chromatography. Then biological activity of rLTB was tested using GM1-ELISA. GCMP was conjugated to rLTB with the chemical method (ADH). Furthermore, the mice were immunized with GAMp-TT/GCMP-TT conjugates and GAMP-TT/GCMP-rLTB conjugates via peritoneal. Finally the anti-polysaccharide antibody was detected. Results The GAMP-TT/GCMP-rLTB conjugate elicits remarkably higher serum antibodies in mice than GAMP-TT/GCMP-TT conjugate. Conclusion These results indicated that polysaccharide conjugates using different proteins as carriers were superior to those using only one protein as carrier.
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Objective To analyze the genome sequencing of mumps virus strain 79 purified from working seeds plague and examine its phylogenetic relationship with wild type virus strain isolated in China,and to explore the efficacy of vaccine at molecular level.Methods Whole genome sequences of two substrains of S79(major and minor),were obtained with fragment amplification by RT-PCR.Genetic distances between S79 and strains identified in China were analyzed based on the phylogenic analysis of small hydrophobic protein(SH) sequences.Results The nucleotide homologies of two S79 substrains(major and minor),with a ratio of 2:5 during culture,with Jeryl Lynn(JL) strain were 99.7% and 100%,respectively.There were scattered non-homologous recombination between two substrains.The genetic distances between strain S79,which was genotype A,and wild type virus strain identified in China,which were genotype F,was 11.2% -20.0%.S79 live vaccine was composed of two substrains,major and minor component,which were highly similar to JL strain in their genome sequences,but different from JL in their ratios during culture.Conclusion Different from wild type virus strain identified in China,the genotype of S79 was A,and phylogenetically distant from other strains,which may account for the low efficacy of S79 live vaccine.The ratios of two substrains might also be of interest for further study of the vaccine protection and efficacy.
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OBJECTIVE: To provide references for the establishment of academic promotion mode in domestic pharmaceutical enterprises. METHODS: The advantage and disadvantages of two chief academic promotion modes were analyzed,and the key points in the the plan for the the academic promotion were exounded. RESULTS & CONCLUSIONS: The self-construction of enterprises and academic promotion outsourcing have their own advantages and disadvantages. Suitable orientation of products and definite product promotion information,the definition of audiences for the promotion,alignment of promotion activity with market orientation,the adaptation of promotion activity to product cycle etc were the keys in making the academic promotion plan. Under the new situation,establishing academic promotion mode suitable for the development of the enterprises is indispensable for the promotion of marketing of prescription drugs.