Objective  To observe disinfection effect and validity period of 75% ethanol used by Chengdu Institute of Biological Products Co., Ltd. Methods  With Staphylococcus aureus, Escherichia coli and Candida albicans as test microorganisms, suspension quantitative germicidal test was used to study germicidal efficacy and validity period of 75% ethanol. Results  The average killing logarithm values of Staphylococcus aureus, Escherichia coli and Candida albicans exposed to 75% ethanol for 1 and 5 min were all >5.00. Disinfection of 75% ethanol was qualified. The average killing logarithm values of Staphylococcus aureus, Escherichia coli and Candida albicans exposed to 75% ethanol stored at room temperature for 7 d for 1 and 5 min were all >5.00. Disinfection of 75% ethanol was qualified. Conclusions  75% ethanol has a good germicidal efficacy for bacteria and fungi.  Disinfection effect of 75% ethanol stored at room temperature for 7 d has not reduced.

Syphilis is a sexually transmitted disease which harms people's health seriously. To understand and to grasp methods for detection of Treponema pallidum have an important significance for discovery and control syphilis in the early stage. This article reviews methods and clinical applications for detection of Treponema pallidum.

 The residual DNA (rDNA) in biological products may be potentially infectious or oncogenic, so purification processes need to be validated for confirming its clearance. It is necessary for manufacturers to show clearance of DNA throughout production processes and to confirm rDNA levels in the final products using an appropriately specific and quantitative analytical method. The most common methodology for rDNA quantitation used currently is a quantitative real-time polymerase chain reaction. In this paper, potential risks of infectivity, oncogenicity, and immunogenicity of rDNA and recent progress in rDNA analysis techniques are reviewed.

 Leishmaniasis is a vector-borne parasitic disease caused by different species of the genus Leishmania, and is endemic in 88 countries on a global scale, with threatening approximately 350 million people. Chemotherapy is a main mean to treat leishmaniasis at present, but the toxicity and drug resistance hamper its application. Therefore development of safe and effective leishmaniasis vaccines is urgent. In the past decades, numerous antigen candidates of Leishmania have been found, but the research progress in clinical trial has been made only in a few vaccines. The advance in research on  leishmaniasis vaccines is reviewed in this paper.

 Bacterial capsular polysaccharide has good immunogenicity and is a major antigen to induce effective immune response, as well as can be used in preparation of polysaccharide vaccines and polysaccharide-protein conjugate vaccines. This review discusses progress in purification technologies and detection methods of bacterial capsular polysaccharide.

Higher quality for the biological products is required in the latest edition of Pharmacopoeia of the People's Republic of China,and the control on the residual host cell protein (HCP) in biological products is more rigorous. Recently, the progress in the research of residual HCP is very rapid. This paper reviews risk analysis and detection strategy of
residual HCP.

 Nucleic acid vaccine is a new type of vaccine, which can deliver foreign genes (DNA or RNA) encoding interest antigens directly into animal cells, produce antigens through host cell expression system, and further induce immune response in the host. It is reported that nucleic acid vaccine is better than protein vaccine because it is immunogenic and safe, and easy to be modified and manufactured. In actual production, nucleic acid vaccine has many advantages, such as easy preparation and purification, short production cycle, low production cost, and easy to form multivalent vaccines. Therefore, it is hopeful that nucleic acid vaccine will become a successful vaccine for human use. This review summarizes research progress of nucleic acid vaccine.

 Nucleic acid vaccines consist of plasmid DNA, viral vectors and RNA vaccines. Since the nucleic acid vaccines combine the benefits of live-attenuated vaccines, and avoid the problems of complication related to live-attenuated vaccine safety and production, they may change the way that next generation vaccines are produced. RNA vaccines, including those based on messenger RNA (mRNA) and self-amplifying RNA replicons, have the potential to break through the limitations of plasmid DNA and viral vectors. With solving the issue of cost and manufacturing feasibility , the commercialization of RNA vaccines has become promising. The concept of RNA vaccines has been demonstrated in humans, and the prospects for further development into commercial products are very encouraging.

 A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. In contrast to the outdated nervous tissue-based techniques for rabies vaccines production, modern techniques of cell culture provide suitable substrates for virus propagation to produce high titer virus and modern high quality rabies vaccine on a large scale. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates in the future.

Over a decade ago, DNA was found to be delivered in vaccine form and elicit an immune response. Four DNA vaccines have been approved to be used in animals. In clinical studies, however, DNA vaccines showed low immunogenic city when inoculation alone. More DNA vaccines for human use will be expected to be brought into the clinic with the improvement in vaccine design and inoculation methods.

 Dengue virus can cause dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In recent years, dengue virus infection is posing a great threat to people’s health. In order to research and develop safe and effective dengue vaccines, the updated biological characteristics and pathogenesis of dengue virus and research advance of dengue virus vaccines are summarized in this review.

Objective  To evaluate immunization effects of two kinds of domestic recombinant hepatitis B vaccines in college freshmen.  Methods  Randomized sampling was adapted in this study. A total of 743 freshmen were divided into recombinant hepatitis B vaccine (CHO cell) group and recombinant hepatitis B vaccine (Hansenula polymorpha) group, and the freshmen in each group were immunized with 3 doses of the corresponding vaccine 10 μg/0.5 ml at a schedule of 0, 1, and 6 months. Serum anti-HBs titer was measured 2 months after the last vaccination, and antibody positive rates and GMC were compared between the two groups.  Results  Antibody positive rates were 87.14% in recombinant hepatitis B vaccine (CHO cell) group and 97.20% in recombinant hepatitis B vaccine (Hansenula polymorpha) group, and anti-HBs GMC was1489.72 and 2265.68 mIU/ml,respectively.  Conclusion  The effects of recombinant hepatitis B vaccine (Hansenula polymorpha) is prominent, which can be used widely.

Objective  To prepare a safe and effective quadrivalent meningococcal polysaccharide conjugate vaccine. Methods  Groups A、C、Y and W135 meningococcal polysaccharide were activated by cyanogen bromide, respectively. With 1,6-adipic acid dihydrazide as linking agent, monovalent meningococcal polysaccharide conjugate vaccines were prepared by carbodiimide-mediated coupling of meningococcal polysaccharide with carrier protein diphtheria toxoid (DT), then groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine (ACYW135-DT) was prepared by mixing each monovalent meningococcal polysaccharide conjugate vaccine in a certain proportion. Mice were immunized with ACYW135-DT, and antibodies to each polysaccharide were detected by indirect ELISA. The statistical analysis of the results were made by t test.  Results  Each index of the prepared ACYW135-DT achieved quality control standard. ACYW135-DT had a good safety and immunogenicity. The levels of IgG antibodies to group A (t=24.487, P＜0.01), group C (t=17.056, P＜0.01), group Y (t=26.213, P＜0.01) and group W135 (t=17.392, P＜0.01) polysaccharides in mice immunized with ACYW135-DT were significantly higher than those in mice immunized quadrivalent meningococcal polysaccharide vaccine.  Conclusion  ACYW135-DT is successfully prepared with this technology.

Genital herpes, a widespread sexually transmitted disease, is caused by herpes simplex virus (HSV) infection.HSV can establish lifelong latent infection in the host and cause severe and recurrent diseases. In addition, HSV infection significantly increases the risk of HIV infection. Although anti-HSV drugs have some effects, they are not capable of preventing reactivation of latent HSV. Therefore, it is urgent to develop effective vaccines to control HSV infection, and limit spread and relapse of the disease. In this paper, the etiology and epidemiology of genital herpes and development progress of genital herpes vaccines are reviewed.

 Human coagulation factor IX (FIX) is a zymogen of a vitamin K-dependent serine protease that plays an important role in the intrinsic blood coagulation cascade. Deficiency or dysfunction of FIX can result in hemophilia B. This article reviews gene and protein structures of FIX as well as research status of FIX therapy for hemophilia B.

Objective  To establish design qualification (DQ) documents of biological product premises conforming to Good Manufacturing Practice for Drugs (GMP) (2010 Revision).  Methods   DQ documents were divided into two parts: protocol and report. The DQs of process layout, manufacturing premises, heating, ventilation and air conditioning systems, clean warm room and clean cold room were discussed.  Results   Through design and qualification, the premises design was proven to comply with the intended use and GMP regulations by documents and records.  Conclusion   The DQ documents of biological product manufacturing premises meeting GMP requirements is established, which lays the foundation for production of safe and effective biological products.

 2013年6月26—28日，美国国立卫生研究院所属的美国国立变态反应与传染病研究所和登革热疫苗倡议组织在美国罗克维尔市组织召开了关于登革热疫苗的咨询会议。会议回顾了登革热疫苗研发的进展，评估了已知的登革热疫苗的保护作用机制，并讨论了未来的研究方向

 Microbiota, composed of deverse microorganism, plays an important role in human health, particularly in the nervous system, endocrine system and immune system. It is found that microbiota is related to several mental disorders. This finding will provide a new way for the treatment of mental disorders. This article reviews studies on the relationship between microbiota and several mental disorders including depressive disorder, anxiety disorder and autism.

 此文介绍了目前国际上使用的三价流感灭活疫苗和流感减毒活疫苗，疫苗接种的方法、效果、安全性、不良反应、禁忌证和成本效益，以及WHO的意见和建议。

  Interleukin-6 (IL-6) is a multifunctional cytokine, which involves in immune responses, hemopoiesis, acute phase reaction, and regulation of bone metabolism. IL-6 receptors are necessary for exerting function of IL-6. More and more researches show that IL-6 overexpression is closely associated with many diseases. Therefore, development of drugs targeted IL-6 has become the main focus of attention. In this paper, structure of the IL-6 and its receptors, functions of IL-6, relationship between IL-6, and diseases and current research of drugs targeted IL-6 are reviewed.

Mucosal immunity covers a variety of mucosal surfaces susceptible to different pathogens. This review explores the basic principles of mucosal immunity in light of the diversity of  mucosal surfaces  and  their  unique  tissue  environments, and offers some thoughts on approaches for developing vaccines to induce mucosal immunity, predominantly based on experiments studying immune responses to infection and vaccination in large animals.

The active vitamin D₃ (1,25-dihydroxyvitamin D₃) is a key regulator for calcium and phosphorus homeostasis. In recent years, a large number of experiments in vitro and
in vivo as well as clinical evidences have showed that the active vitamin D₃ has important antiinflammatory and immunomodulatory effects. This review summarizes the regulatory effects of active vitamin D₃ on immune system and immune- related diseases.

 载脂蛋白A1(ApoAl)作为人体血浆高密度脂蛋白分子中载脂蛋白的主要成分,在人体生理和病理过程中发挥着重要的作用.早年的研究表明,它具有胆固醇逆向转运功能,从而对动脉粥样硬化有抵抗与治疗作用.最近研究表明,它还具有其他生化作用,包括抗氧化作用、抗炎、抗内毒素作用等.这些功能的发现将促使ApoA1成为临床上防治动脉粥样硬化、炎症及内毒素血症等的新方法.本文就ApoA1的结构与功能、分离纯化以及临床意义等方面的研究进展作一综述.

Objective  To understand serum positive rates of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV) in 178 neonats and their relationship with clinical manifestation of premature infants.  Methods  A total of 178 neonatal serum samples were collected, including 114 umbilical cord sera from normally delivered newborns and 64 blood sera from premature infants. IgG and IgM antibodies to HSV-1 and HCMV were detected with ELISA. The χ² test was adopted for the comparisons. Results  In 178 neonats, HSV-1 IgG and IgM positive rates were 83.70% and 0.00%, HCMV IgG and IgM positive were 94.38% and 0.56%, respectively. In 114 normally delivered newborns, HSV-1 IgG and IgM positive rates were 78.07% and 0.00%, HCMV IgG and IgM positive were 94.74% and 0.88%, respectively. The positive rate of both HSV-1 IgG and HCMV IgG was 73.68%. In 64 premature infants, HSV-1 IgG and IgM positive rates were 93.75% and 0.00%, HCMV IgG and IgM positive rates were 93.75% and 0.00%, respectively. The positive rate of both HSV-1 IgG and HCMV IgG was 87.50%. The HCMV IgG positive rates between premature and normally delivered neonates were not statistically significant (χ²= 0.07, P>0.05); while HSV-1 IgG positive rate and both HSV-1 IgG and HCMV IgG positive rate in premature neonates were significantly higher than those in normally delivered newborns (χ²=7.38, 4.65,  P<0.05). The premature infants with HSV-1 IgG and HCMV IgG positive had higher risk of premature rupture of membranes, placental abruption, oligohydramnios, amniotic fluid contamination and skin abnormalities. Conclusions  The positive rates of HSV-1 IgG and HCMV IgG are high in neonates. The premature infants with HSV-1 IgG and HCMV IgG positive may be associated with premature rupture of membranes and other clinical manifestations.

There are promising prospects for IgG-format bispecific antibodies in applications of cancer therapy. In early experiments，bispecific IgG created by quadromas or coexpression of two IgG had poor production yields and could not be purified easily. Recently, there are many technologies for constructing bispecific IgG. This review describes the latest progress in various approaches to the engineering of bispecific IgG.

Objective  To compare the difference of mean osmolalities among 6 viral vaccines and observe lot-to-lot stability of a single vaccine, and provide a basis for increasing an approach of quality control of viral vaccines. Method  The osmolalities of 5 live attenuated viral vaccines (measles, mumps and rubella combined vaccine, measles and mumps combined vaccine, measles vaccine, rubella vaccine, varicella vaccine) and influenza vaccine (split virion) were determined by a method of freezing point depression. Coefficient of variation was calculated. The mean osmolality of measles, mumps and rubella combined vaccine was used as a control and mean osmolalities of the remaining 5 vaccines were compared with the control by homogeneity test of variance and hypothesis test. Results  There was no significant difference of mean osmolalities between measles and mumps combined vaccine and the control (t=1.66, P>0.05). The mean osmolalities of measles vaccine, rubella vaccine, varicella vaccine, and influenza vaccine were significantly different from that of the control (Z>1.96，P<0.001). The lot-to-lot stability of a single vaccine was good. None of the coefficients of variation were more than 3%, and the measurements ranged between 90% and 110% of the mean values. Conclusions There are some differences of the osmolalities among 6 viral vaccines, but lot-to-lot stability of a single vaccine is satisfactory. Therefore, corresponding criteria should be set for different vaccines.

 Process validation is not only legal and regulatory requirements for vaccine industry, but also important means of quality assurance and essential conditions for commercial production. With development of the vaccine industry as well as publication of the latest industry regulatory guidelines, process validation has been given new contents and related to all stages of the product life cycle. Based on the latest industry guidelines and some practical work experience, the latest contents and trends of process validation are reviewed in this article.

Objective  To evaluate efficiency of plague component vaccines by detection of mice serum antibody titer and observation of protecting guinea pigs against virulent
Yersinia pestis challenge.  Methods  The plague component vaccines were prepared by admixing 15 μg F1 antigen, 15 μg rV antigen and 15 μg F1+15 μg rV antigen with aluminum hydroxide adjuvant, respectively. NIH mice and guinea pigs were immunized with 2 doses of plague component vaccines subcutaneously at a schedule of 0 and 2 weeks. the animals were immunized with one dose of live attenuated plague vaccine for percutaneous scarification as a control group. Serum anti-F1 and anti-rV IgG titers in mice were determined by indirect ELISA 6 weeks after immunization, and guinea pigs were subcutaneously challenged with virulent Y. pestis strain 141 to observe the efficiency of the plague component vaccines.  t test was adopted in the comparison between the groups.Results  The results of antibody determination showed that anti-F1 IgG or/and anti-rV IgG levels in three plague component vaccine groups were much higher than those in live attenuated plague vaccine group(t=3.041,3.472,15.958,16.264,p<0.01). The results of challenge test in guinea pigs showed that survival rate in F1+rV vaccine group was 90 % (9 / 10), and those in F1 vaccine group and rV vaccine group were 50 % (5 / 10) and 20 % (2 / 10), respectively.  Conclusions  The plague F1+rV vaccine is effective for preventing plague, and F1 vaccine or rV vaccine is unable to provide effective protection against virulent Y. pestis challenge.

Probiotics are ubiquitous in every habitat on earth, which was recognized as a "gut health guardian." It can improve human health by maintaining the balance of the host commensal bacteria, affecting the intestinal barrier function and modulating immune response. Some probiotics can enhance immune function, inhibit carcinogens, and affect gene expression in tumor cells, thus having antagonistic effects on tumors. In the future, probiotics will have a good application in tumor prophylactics and therapy.

 Human epidermal growth factor 3 (human epidermal growth factor receptor 3, HER3) is a type I transmembrane tyrosine kinase receptors. HER3 gene expression is up-regulated in a variety of tumors. This article briefly reviews the structural characteristics of HER3, the relationship between HER3 and tumorigenesis and anti-tumor effect of antibody against HER3.

 Human respiratory syncytial virus (RSV) is an important pathogen responsible for bronchitis and pneumonia in young children. No safe and effective vaccines are available so far. Great progress has been made in molecular biology, epidemiology, and pathogenic mechanism of RSV during the past several decades. In this paper, virological and epidemiological characteristics, and vaccine development strategies of RSV are reviewed.

Objective  To prepare groups A and C meningococcal polysaccharide (PS) conjugate vaccine with outer membrane protein (OMP) of group B meningococcus as a carrier (AC-OMP), and preliminarily study on stability of the preparation process for AC-OMP. Methods  Groups A and C meningococcal polysaccharides activated by cyanogen bromide were coupled with OMP of group B meningococcus respectively to prepare monovalent A-OMP and C-OMP, then AC-OMP was prepared by mixing monovalent A-OMP and C-OMP. The prepared AC-OMP was detected according to the requirements of Chinese Pharmacopoeia 2010 (Volume Ⅲ). Mice were immunized with the prepared AC-OMP, and seroconversion rates of anti-PS in immunized mice were detected by ELISA. Results  Each index of the prepared AC-OMP achieved quality control standard. AC-OMP had a good immunogenicity, and seroconversion rates of anti-PS were 100% in immunized mice. Conclusion  The preparation process is suitable for AC-OMP.

近年来,结核病有卷土重来之势,新型结核病疫苗领域的研究日益受到人们的关注,而寻找结核杆菌保护性抗原成分则是研究的重点.本文就保护性抗原的可能作用机制、保护性抗原的种类及研发结核病疫苗所面临的问题予以综述.
 

腺相关病毒(AAV)是基因治疗中最有希望的载体之一,它具有非致病性、对宿主免疫原性弱及广泛的细胞和组织亲嗜性等优点.本文着重探讨了AAV的血清分型与高滴度表达抑制转录因子的重组AAV的制备,并综述了AAV在基因治疗糖尿病及心血管病中的最新研究进展.

Lactic acid bacteria (LAB) are food-grade, generally regarded as safe microorganisms. Effective immune responses can be induced using LAB as expression vectors for antigen expression. Oral and intranasal immunizations can also induce mucosal immune response. They are easy to operate and have better immune efficacy and compliance than those achieved by traditional injective way. In the present review, we describe advantages of LAB as vectors,  various delivery systems developed by LAB, successfully expressed heterologous proteins, and a novel delivery system—Gram-positive enhancer matrix particle.

 The interaction between T and B lymphocytes is the key to induce the adaptive immune response, in which the coordination of CD40 and CD40L not only has an important regulation for humoral and cellular immunity, but also plays a major role in anti-infection, anti-virus and anti-tumor immune responses as well as inflammatory reaction. CD40 is mainly expressed on the surface of B cells, professional antigen-presenting cells and some of tumor cells. Therefore, CD40-induced signal pathway may relate to many types of malignant tumors, autoimmune diseases and immunodeficiency diseases. CD40-targeted therapy as tumor immunotherapy has become one of focuses in immunological study. In this review, the biologic features and functions of CD40, CD40-related malignancies, and application of therapeutic anti-CD40 monoclonal antibodies to tumor therapy are summarized.