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Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.

Objective: To evaluate the immunogenicity of inactivated quadrivalent influenza vaccine (QIV) in adults aged 18-64 years, through a Meta-analysis. Methods: Literature was retrieved by searching the Medline, Cochrane Library, Science Direct in the past decade. All the studies were under random control trial (RCT) and including data related to immunogenicity which involving sero-protection rate (SPR) and sero-conversion rate (SCR) of the QIV, versus inactivated trivalent influenza vaccine (TIV) in the population aged 18 to 64. Revman 5.3 software was employed to manipulate the pooled date of the included literature. Result: A total of 8 studies for the SPR and SCR of the shared strains (two A lineage and one B lineage) were included. There appeared no significant differences in the response rates between the two vaccines. As for QIV versus TIV (B/Yamagata), the pooled RR of the SPR for B/Victoria was 1.28 (95 %CI : 1.08-1.51, P <0.05), with the pooled RR of the SCR for B/Victoria as 1.94 (95 %CI : 1.50-2.50, P <0.05). For QIV versus TIV (B/Victoria), the pooled RR of the SPR for B/Yamagata as 1.10 (95 %CI : 1.02-1.18, P <0.05), and the pooled RR of SCR for B/Yamagata as 1.99 (95 %CI : 1.34-2.97, P <0.05). Conclusion: In the population aged 18-64 years, inactivated QIV was equivalently immunogenic against the shared three strains included in the activated TIV while a superior immunogenic effect was noticed in the vaccine strain which did not include the inactivated QIV.

Objective: To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults. Methods: The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults. Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine, could be contacted and were sero-negative before primary vaccination. All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine. The blood samples were collected before booster dose vaccination and 28 days after the immunization. Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus. Results: The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml, respectively, and the sero-protection rates were 94.7 % and 65.0 % , respectively. After the vaccination of the booster dose, the sero-protection rates in both groups were 100.0 % , and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml, respectively. Conclusion: The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination. However, the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group. Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

The rapid mutation and widely spread of duck hepatitis A virus (DHAV) lead to the vast economic loss of the duck industry. To prepare and evaluate bivalent inactivated vaccine laboratory products of DHAV, 6 strains were screened from 201 DHAV-1 strains and 38 DHAV-3 strains by using serotype epidemiological analysis in most of the duck factory. Vaccine candidate strains were selected by ELD50 and LD50 tests in the 6 strains. Continuously passaged, the 5th passaged duck embryos bodies grinding fluid was selected as vaccine virus seeds. The virus seeds were treated with formaldehyde and water in oil in water (W/O/W) emulsions, making into three batches of two bivalent inactivated vaccine laboratory products. The safety test, antibody neutralization test, challenged protection and cross immune protection experiment suggested that the vaccines possessed good safety, and neutralizing antibodies were detected at 7th day and the challenged protection rate reached 90% to 100% at the 14th and 21st day. Moreover, immune duration of ducklings lasted more than five weeks. However, cross-immunity protection experiments with DHAV-SH and DHAV-FS only had 20%-30%. The two bivalent inactivated vaccine laboratory products of duck viral hepatitis were effective and reliable, providing a new method as well as a new product for DHAV prevention and control.

Thymopentin (TP5) and bursopentin (BP5) are both immunopotentiators. To explore whether the TP5-BP5 fusion peptide (TBP5) has adjuvant activity or not, we cloned the TBP5 gene and confirmed that the TBP5 gene in a recombinant prokaryotic expression plasmid was successfully expressed in Escherichia coli BL21. TBP5 significantly promoted the proliferation of thymic and splenic lymphocytes of mice. The potential adjuvant activity of the TBP5 was examined in mice by coinjecting TBP5 and H9N2 avian influenza virus (AIV) inactivated vaccine. HI antibody titers, HA antibodies and cytokines levels (IL-4 and IFN-γ) were determined. We found that TBP5 markedly elevated serum HI titers and HA antibody levels, induced the secretion of both IL-4 and IFN-γ cytokines. Furthermore, virus challenge experiments confirmed that TBP5 contributed to inhibition replication of the virus [H9N2 AIV (A/chicken/Jiangsu/NJ07/05)] from mouse lungs. Altogether, these findings suggest that TBP5 may be an effective adjuvant for avian vaccine and that this study provides a reference for further research on new vaccine adjuvants.

Objective: To investigate the impact of the injection of inactivated vaccine for hemorrhage of Grass carp on the expressions of main immune-related genes in spleen including immunoglobulin M (IgM), major histocompatibility complexI(MHC I), interferon I(IFN1), complement 3 (C3), interleukin-1β (IL-1β) and intelectin genes., Methods: Ctenopharyngoden idellus kidney (CIK) cells were inoculated with Grass carp reovirus (GCRV). Then inactivated vaccine was prepared by inactivating virus suspension with formaldehyde. Vaccine was 50- and 100-times diluted with normal saline. The experiments included four groups: undiluted group, 50-times diluted group, 100-times diluted group and normal saline control group. Then healthy Grass carps with the average body mass (20 ± 5) g were intraperitoneally injected with vaccine or normal saline separately for each group. Spleens were collected at different time points after injection (0, 6, 12, 24, 72 hours) and total RNA extraction was performed immediately. Real-time quantitative PCR (qRT-PCR) was used to detect mRNA expressions of the six immune-related genes., Results: Compared with normal saline control group, inactivated vaccine injection increased mRNA expressions of the six immune-related genes in the spleen of Grass carp, indicating that the vaccine stimulated the Grass carp to generate non-specific and specific immune responses. In the immunized groups, relative expressions of the genes intelectin, MHCI, IL-1β, C3 were all up-regulated at first and then declined as time went on. Relative expression of IFNIgene reached the peak at 6 hours post-injection and then decreased gradually to the normal level. Differently, relative expression of IgM gene increased continuously within 0-72 hours post-injection., Conclusion: The expressions of the six major immune-related genes were all up-regulated in the spleen of Grass carp injected with different doses of inactivated vaccine for hemorrhage of Grass carp.

Objective: To evaluate the safety and immunogenicity of seasonal inactivated influenza vaccine (split virion) and to analyze its cross-reactive antibody responses to H7N9 avian influenza virus., Methods: An open-labeled clinical trial was carried out in infants aged 6-35 months, adults aged 18-60 years and the elderly aged >60 years. After vaccinations (one dose for adults and the elderly and two doses for infants), adverse events were observed. Serum samples were obtained before vaccination and 21 days after vaccination from adults and elderly subjects. Three types of antibody against seasonal influenza virus and antibody against H7N9 avian influenza virus were tested using microhemagglutination inhibition (HI) assay. Immunogenicity of the vaccine was evaluated based on the immunogenicity criteria for adults and the elderly, set by the Committee for Medicinal Products for Human Use (CHMP) for the European Medicines Agency., Results: A total of 202 subjects (65 infants, 69 adults and 68 elderly) were enrolled and injected for at least one dose. The overall rate of adverse events was 12.4% (25/202) and most of them were under systemic reaction. No serious adverse event was reported. Pre- and post-vaccination serum samples were collected from 124 subjects (64 adults, 60 elderly). After 21 days of vaccination, the sero-conversion rate, sero-protection rate, and geometric mean titer (GMT) ratio (post-/pre-vaccination) of antibody against seasonal influenza virus were 78.1%-90.6%, 92.2%-100.0% and 7.9-41.0 among adults while 66.7%-83.3%, 86.7%-100.0% and 5.7-20.4 among the elderly, respectively. However, after vaccination, both sero-conversion rate and sero-protection rate of antibody against H7N9 avian influenza virus among adults and the elderly became zero, with GMT ratio between 1.2 and 1.4., Conclusion: This trial vaccine appeared to have good safety and immunogenicity but inducing no cross-reactive antibody response to H7N9 avian influenza virus.

This study aims to construct inactivated coxsackievirus A16 (CVA16) vaccine and to investigate its protective effect in ICR mice. A clinical isolate of CVA16, 521-01T, was cultured in VERO cells, inactivated by formaldehyde, and purified by ultracentrifugation for vaccine preparation. Purity and other characteristics of the vaccine were determined by SDS-PAGE and Western blot. Female ICR mice were subcutaneously inoculated with inactivated CVA16 or Al(OH)3-absorbed CVA16, followed by booster immunization at the end of 2 and 4 weeks. CVA16-specific IgG titers in serum were determined by ELISA, and titers of neutralizing antibodies were determined by viral neutralization assay. The immunity of T lymphocytes was evaluated by IFN-gamma ELISPOT assay. The protective effect was evaluated by challenging the neonatal offspring (< 48 hours) of vaccinated female mice with 1 000 LD50 of CVA16 521-01T. The mortality rates of different groups were compared. The results showed that Al(OH)3 +CVA16 could induce high titers of specific IgG antibodies in ICR mice. After being boosted two times, the serum IgG antibody titer could reach up to 1 : 1 x 10(5) (P = 0.000), and neutralizing antibody titer was higher than 1 : 256. Additionally, more spot forming cells were induced in the immunized groups than in the negative controls. The maternal antibodies showed protective effect in 100% of the neonatal mice challenged with 1 000 LD50 of CVA16 521-01T. The inactivated CVA16 vaccine has ideal immunogenicity and immunoprotective effect. This research lays a foundation for the development and evaluation of CVA16 vaccines.

Objective: To evaluate the safety of both domestic live attenuated and inactivated hepatitis A vaccines, and to provide reference for emergent vaccination after hepatitis A outbreaks., Methods: 493 children aged 6 - 9 with negative antibody to HAV (produced by Abbott) were randomly divided into four groups as vaccinated with domestic live attenuated hepatitis A vaccine (Group A), domestic inactivated hepatitis A vaccine (Group B), imported inactivated hepatitis A vaccine (Group C) and hepatitis B vaccine (Group D) respectively. Adverse events following the immunization were observed 30 minutes, 24, 48 and 72 hours after the vaccination, under double-blind method., Results: The main AEFIs were: fever, local pain and scleroma but no other severe AEFIs were observed. The rates of AEFIs were 13.95% in Group A, 15.25% in group B, 16.80% in group C and 25.62% in group D, with no statistical differences between these groups (χ(2) = 6.953, P > 0.05). 2 weeks after the vaccination, the positive conversion rates of domestic live attenuated hepatitis A vaccine and domestic inactivated hepatitis A vaccine were 85.0% and 94.59% respectively. The rate of domestic inactivated hepatitis A vaccine reached 100% at 4 weeks after the vaccination. The antibody levels of HAV-IgG of Group A and B in 2, 4 and 12 weeks of vaccination and of Group C were higher than that of Group D. After 12 weeks of vaccination, the antibody level of group B became higher than it was Group C., Conclusion: There were no differences on safety among domestic live attenuated hepatitis A vaccine, domestic inactivated hepatitis A vaccine or imported inactivated hepatitis A vaccine under routine or emergency vaccination. All the vaccines showed satisfactory effects.

Influenza, caused by influenza virus, is a serious respiratory illness which poses a global public health threat. Vaccination is the primary strategy for the prevention and control of influenza. Although both inactivated vaccines and the live attenuated vaccines are effective in preventing influenza, the current vaccines have poor efficacy in the elderly and fail to provide protection against heterosubtype viruses. Development of a safer and more effective influenza vaccine that provides broad cross protection, overcoming the intrinsic limitation of the current vaccines, has been a scientific challenge. During the past decades, structural biology, reverse genetic and other virological technologies developed quickly and sped the progress of influenza vaccinology. Some new strategies for developing influenza vaccine have been generated, produced encouraging results, which showed great prospect as next-generation of influenza vaccines.

Objective: To evaluate the safety of enterovirus type 71 (EV71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions., Methods: In the neonatal monkey model for EV71 vaccine protection, vaccinated group (n = 4) and unvaccinated group (n = 4) were attacked with live virus at the same time, the parameters of clinical observations, antibodies and inflammatory factors in peripheral blood and cerebrospinal fluid (CSF) were detected. And the pathological changes in major organs were used to determine the patho-inflammatory reactions during the immune responses elicited by vaccination., Results: The neutralizing antibodies of vaccine group reach to 1:32. There was no obvious changes of inflammatory factors in peripheral blood and CSF of monkeys challenged or unchallenged by live virus. In peripheral blood of unvaccinated group, the level of basophilic granulocyte higher 4 - 5 times than normal level and the interferon-γ (IFN-γ) showed obvious increase. Live virus infected after 7 days, the interleukin-6 (IL-6) and IFN-γ in peripheral blood of unvaccinated group (18.5, 12.7 pg/ml) were higher than vaccinated group (10.2, 7.6 pg/ml). Furthermore, the IL-6 in CSF (102.0 pg/ml) had 4 - 5 times increased than vaccinated group (12.4 pg/ml) at 7 days after virus exposure. Meanwhile, the pathological analysis revealed that no obvious changes were detected in CNS and other organs of vaccinated monkeys challenged with live virus. However, the pathological damages induced by virus infection could be determined in the unvaccinated control monkeys, including neuronal damage, massive cellular infiltration associated with pulmonary edema/hemorrhage and pulmonary/bronchial damage due to an infiltration of inflammatory cells., Conclusion: Capable of inducing an immune response, the EV71 inactivated vaccine offers protection to neonatal rhesus monkeys against the attacks of live virus. Based on the results of no patho-inflammatory reaction and pathological damage after viral infection in vaccinated animals, the excellent safety of this vaccine may be confirmed in neonatal monkey.

Anthrax is a zoonosis caused by Bacillus anthracis, which seriously affects human health. In recent years, a special phenomenon is found that the metabolic active of a bacterium remains after it is killed. To development of a KBMA (killed but metabolically active) Bacillus anthracis vaccine candidate strain, a plasmid pMAD and a recombinase system Cre-loxP were used to knockout the uvrAB gene of B. anthracis AP422 which lacks both of two plasmids pXO1 and pXO2. The results of PCR and RT-PCR shows that uvrAB genes were deleted from B. anthracis AP422 chromosome successfully. The constructed B. anthracis AP422deltauvrAB was inactivated by photochemical treatment (PCT) including an exposure in a long-wave-length ultraviolet (UVA) light and a treatment of 8-Methoxypsoralen (8-MOP), then the metabolic activity were detected by the method of MTS. The results showed that the killed B. anthracis AP422deltauvrAB maintained a highly metabolic activity for at least 4 hours, showing a state of KBMA. The KBMA strain of B. anthracis AP422deltauvrAB provides the prospective vaccine candidate strain for anthrax.

EV71 infection has become a serious public health threat especially among young children. Yet, at present, no specific antiviral drug against EV71 infection is available. A number of scientists are studying various kinds of vaccines, including inactivated vaccine, virus-like particle vaccine, DNA vaccine, synthetic peptide vaccines, and transgenic oral vaccine. This article reviews the recent advancement in the design of various kinds of vaccine against EV71 as well as their prospective usefulness, effectiveness, weakness and developments in the foreground.

Objectives: To summary and compare the different seroconversion rates after the primary vaccination for the Japanese encephalitis (JE), and to evaluate the serological effect of 3 kinds of JE vaccines., Method: Searching "CHKD", "Wanfang" database and "EMCC" databases, the studies of the immunogenicity after the primary JEV vaccination, all randomized controlled trials or non-randomized controlled trials were included, and statistical analysis were made by RevMan 4.2.10 software., Results: A total of 12 literatures were included, 7 studies had control groups. The seroconversion rates after the primary vaccination, JEV-L, JEV-I (Vero) and JEV-I (PHK), were 86% (95% CI: 80%-91%), 83% (95% CI: 72% -94%) and 64% (95% CI: 58%-69%) respectively. Comparing the seroconversion rates of the 3 kinds of vaccines after primary immunization, the rate of JEV-I (Vero) was significantly higher than the rate of JEV-I (PHK), other comparisons were no significant difference., Conclusion: The serological effects of JEV-L and JEV-I (Vero) after the primary vaccination were higher than that of JEV-I (PHK).

Objective: In order to observe the safety and neutralizing antibody response to purified inactivated Japanese encephalitis vaccine (primary hamster kidney cell, PHK)., Methods: Phase I, II, III field trials were performed and 943 healthy volunteers aged from 6 months to 10 years were administrated the JEV-I (PHK) vaccine at day 0 and day 7 respectively., Results: The vaccine did not cause any severe systemic and local adverse reactions. In phase I, 40 healthy volunteers were inoculated and the total reaction rate was 2.5%. In phase II and III, 903 healthy volunteers were inoculated JEV-I (PHK) and 101 healthy volunteers were inoculated with the Vero cell-derived JEV vaccine, the total adverse reaction rates were 6.2% and 14.2% respectively. The positive sero conversion rates of neutralizing antibody to the test and the control vaccine in antibody negative group were 96.9% (Geometric Mean Titers, GMT1:32.8) and 84.0% (GMT1:43.9) respectively and in antibody positive group were 93.1% (GMT1:167.2) and 100% (GMT1:181.0) respectively., Conclusion: The JEV-I (PHK) vaccine is safe and effective. Trial Registration National Food drugs surveillance administrative bureau, "Medicine Clinical Experiment Written Directive from a Superior" number: 2003L00429.

Hepatitis A is one of the global public health problems, and China has high prevalence. In order to decrease the incidence of hepatitis A, China has integrated Hepatitis A vaccine into Expanded Program on Immunization (EPI) in 2007. The paper will provide some ideas on the immunogenicity and impact factors of the different types of hepatitis A vaccines that are used in China.

Objective: To study the antibody persistence of live attenuated hepatitits A vaccine, and to compare the antibody between with inactivated vaccine., Methods: 211 HAV susceptible children were divided randomly into three groups, Group A was injected three doses HepA-L at 0, 6 and 12 monthes; Group B was administrated two dose HepA-L at 0 and 6 months, and group C was immunized with inactivated vaccine at month 0 and 6. Serum samples were detected for Anti-HAV at 1, 6, 7, 12, 13, 24, 84 months after vaccination in each group., Results: The seroconversion rates reached 100% after 2nd dose in all groups. The highest GMC was 2938.1 mlU/ml, founded in group C, and it was 1315.6 mlU/ml and 1586 mlU/ml in group A and B respectively. After the 3rd dose at month 12 in group A, the antibody increased dramatic, which reached 1945.3 mlU/ml. 84 months after first dose in each group, the antibody can be detected from all subjects. Though the GMC in group A declined to 336.8 mlU/ml, it was significant higher than that in group B and C., Conclusion: The good booster effect with HepA-L was well observed in a short-term. The immune response induced by 2 to 3 doses HepA-L could compete with inactivated hepatitis A vaccine. However, long-term effects of both vaccines need further study.

Objective: To understand the epidemiological characteristics and the influencing factors of Japanese encephalitis (Abbreviated JE) at different periods in Hainan province, and to provide evidence for JE control strategies., Methods: Data on JE had been collected since 1952 and related incidence, mortality, fatality rates of JE and the rate of JE vaccination were calculated for four periods: the natural epidemic period (1952-1978), period for inactivated JE vaccine promotion (1979-1986), national immunization program period (1987-1990) and the promotion of live-attenuated JE vaccine period (1991-2007). History on the immunity of JE and data from the monitoring programs on cases and insect vectors were also analyzed., Results: The average annual incidence in natural epidemic period was 7.12/100,000, which was also the highest among the 4 periods with the mortality rate as 0.89/100,000. The average annual incidence was 0.11/100,000 which was the lowest while the mortality rate was 0.01/100,000 in the period when live-attenuated JE vaccination was under promotion. Since the establishment of JE surveillance system was set up in Hainan province in 2002, the specimen collection rate of JE reported suspected cases had reached 92.8%, while the incidence of confirmed JE cases fluctuated between 0.05/100,000 and 0.2/100,000. Of the confirmed cases, 86% did not have clear history of JE vaccination. The annual average protective rate reached 95.69% in 2004-2007. The density of insect vectors was high in Hainan province. The infection rate of JE in host animal swine, kept rising from April to October, and in some surveillance points, the rate reached 99.3%. The density of insect vector plotted in trans-curve with the infection of host animals., Conclusion: The application of live-attenuated JE vaccine was found to have had significant protective effect on JE in susceptible children. It helped reducing the incidence and controlling the epidemics of JE. It appears feasible to include live-attenuated JE vaccine into the expanded immunization program.

Objective: To prepare a vaccine with inactivated Feline Panleukopenia Virus (FPV) isolated from Siberian tigers and to evaluate its immunological effect., Methods: FPV-HLJ, an FPV strain previously isolated from Siberian tiger in our lab was used to inoculate cat kidney cell line F81 with dose 1/10(v/v) using the synchronizing inoculation method. Inoculated F81 cell line was cultured at 37 degrees C and collected when cytopathic effect was up to 75%. Viral suspension was inactivated by using formaldehyde for 24 h and inactive vaccine preapred by adding aluminium hydroxide gel as adjuvant to the suspension. The inactive vaccine was applied to 2-month-old kitten tigers of hypodermically after protection effect was proved in 2-month-old nonimmunized cats by using the same vaccination procedure., Results: Antibody level in vaccinated cats revealed an increasing trend that the valence of antibody reached 1:1024-2048 after three times of vaccination. All vaccinated cats survived challenges of virulent FPV virus. The valence of antibody reached 1:1024 in most vaccinated tigers 15 days after the third vaccination., Conclusion: The results indicated that the inactivated vaccine can produce immunoprotection for tigers.

Objective: To understand the effectiveness of inactivated influenza vaccines (IIV)., Methods: We did a Meta analysis on IIV effectiveness with papers published during March 1998 and May 2008 in Chinese journals, using fixed model or random model according to the heterogeneity of the studies., Results: A total number of 13 studies were included, of which 11 were cohort studies and 2 were randomized controlled trials. Through Meta analysis on cohort studies regarding the effectiveness against influenza like illness (ILI), we noticed that the effectiveness of the vaccine was 66% (95% CI: 51%-76%) in children and adolescents, but 47% (25%-63%) in adults, and 53% (20%-72%) in the elderly., Conclusion: IIV was effective in protecting against influenza like illness.

Aim: To prepare monoclonal antibody (mAb) against Vibrio cholerae O139, which would be used as the gold colloidal reagent strip for rapid detection of O139, and to determine its biological characterization., Methods: BALB/c mice were immunized by inactivated Vibrio cholerae O139. Anti-O139 mAbs were prepared by using hybridoma technique. The specificity of mAb was determined by indirect ELISA and Western blot. The indirect ELISA was used to identify Ig subgroup, detect its titer in ascites and relative affinity, and analyze antigen-binding epitope of mAbs., Results: Two hybridoma cells (O4D7 and O4D10), secreting anti-O139 mAbs were obtained. The Ig subgroups of O4D7 and O4D10 were IgG2b and IgG3, respectively. The mAb's titer in ascites was 1:10(7). The relative affinity of mAb O4D7 was more than 10(5) and that of O4D10 was more than 10(4). The result of additive ELISA showed that two mAbs could recognize different antigen epitopes., Conclusion: The successful preparation of two anti-O139 mAbs provides a powerful tool for the development of a rapid method of detecting Vibrio cholerae O139 infection.

Objective: To evaluate the safety and immunogenicity of influenza split vaccine., Methods: According to the criteria of No.2002SL0043, instruction of application for new drug in clinical trial issued by the State Food and Drug Administration, 876 healthy persons were divided at random into vaccine group and control group. The trial was performed with the double blind method. Local and systemic adverse reactions were observed within 3 days after the vaccine group subjects were vaccinated. The antibody response to vaccines was detected with hemagglutination inhibition (HI) test. Numbers of seroconversions and HI titers greater than or equal to 40, as well as the mean geometric titer increase in HI were analyzed., Results: There was no significant difference in local and systemic adverse reaction between vaccine and control groups. Meanwhile there was also no significant difference in seroconversions and protective level between two groups. However, there was obvious difference in mean geometric titer increase of antibody against H1N1 virus, while there was no significant difference in that of antibodies to H3N2 and type B viruses., Conclusions: The safety and immunogenicity of both vaccines are excellent.

Objective: To summarize and analyze the epidemic situation of hantaviruses including geographic distribution, types and prevalent intensity of epidemic areas of hantavirus for the last 30 years in China, and to discuss relative preventive measures., Methods: Collecting and analyzing the data of hantaviruses epidemics in China., Results: The annual number of cases of hantavirus disease rapidly increased from 3295 in 1970 to 115,804 in 1986 then sustained between 40,000 and 60,000 cases annually in the 1990's, and then decreased thereafter. The epidemic areas existed in all provinces except Qinhai and Xinjiang and there were the hospitalized cases of hantavirus disease reported in other provinces. In recent years, the prevalence of hantavirus infection had increased in some cities, and the seasonal distribution of the cases changed as well., Conclusion: Data suggested that the new epidemic characteristics of hantaviruses had emerged in China suggesting that it was necessary to strengthen surveillance programs and to take comprehensive preventive measures for the control and prevention of hantaviruses in China.

Objective: To evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children., Methods: A total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose., Results: The vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml., Conclusion: GMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.

Objective: To compare the reactogenicity and serology between influenza subunit vaccine and split vaccine., Methods: A randomized, double-blind study was carried out among children (age 6 - 12 years) in order to compare the safety and immunogenicity of an influenza inactivated subunit vaccine (Agrippal, Chiron Vaccines) with that of a split vaccine (Flurix, GSK)., Results: A total of 499 subjects were vaccinated and included in the safety analysis. A total of 249 subjects received Agrippal and 250 received Flurix. All subjects were kept under medical observation for 30 minutes in order to check the evidence of having any immediate local and systemic reaction. Daily observation records were collected during the 3-day follow-up after vaccination. 6.4% of the cases with fever >or= 37.5 degrees C was reported in the Flurix group, but 2.4% in Agrippal group which was significantly less than the former group (P > 0.05). Blood samples (the D0 pre- and D23 post-vaccination sera) were collected from 224 of Agrippal group and 223 of Flurix group and analysed by the haemagglutination inhibition (HI) assay. Agrippal and Flurix induced similar seroprotection (HI titer >or= 1:40, H1N1 99.6% vs 100.0%; H3N2 99.1% vs 99.1%) and seroconversion (4-fold increase, 95.1% vs 97.8%; H3N2 74.5% vs 79.8%) rates and geometric mean titer (GMT) increase (16.0 vs 21.0; 5.4 vs 6.4) against the two A subtypes. A similar seroprotection rate (94.2% vs 96.4%) and GMT increase (21.2 vs 18.2) against the influenza B strain were also noticed in both vaccines. No significant difference was found in the results of immunological assay between the two vaccines (P < 0.05). A lower seroconversion rate against B strain was observed in Agrippal group than in Flurix group (91.1% vs 97.3%)., Conclusion: In terms of safety, both vaccines were generally well tolerated. The fever reaction was less frequently seen in the Agrippal group. Both vaccines induced an effective immune response in the vaccines.

Objective: To adapt the candidate strains of hemorrhagic fever with renal syndrome (HFRS) purified vaccine to Vero cells and to study their antigenicity and immunogenicity., Methods: The viral strains H8207 (Hantaan virus, HTN) and Y86013 (Seoul virus, SEO) were continuously propagated in Vero cell by the terminal dilution method and studied the characteristics of virus multiplication, viral titers and the amounts of virus antigen after serial passages. Three batches of crude monovalent inactivated vaccine were developed using the different passages of these 2 viral strains., Results: The strains H8207 and Y86013 adapted to Vero cells and stably grew on the cells with high titers. Rabbits immunized with the crude vaccines of H8207 and Y86013 showed 100% sero-conversion and the neutralizing antibody titers of the rabbit immune sera reached 1?10 at 4 weeks after 2 times of immunization., Conclusions: The results suggest that these 2 candidate strains had adapted to Vero cells, possessed high titers and good immunogenicity and be feasible to prepare the HFRS purified vaccine in Vero cells.

Objective: Using the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine., Methods: Observing the safety and immune effects of different groups., Results: Data on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05)., Conclusion: Results showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.

Objective: To evaluate safety and immunogenicity of inactivated hepatitis A vaccine in HBsAg carriers and healthy children., Methods: One hundred and twenty-one healthy children and ten HBsAg carriers, aged 1-10 years HAV susceptible were enrolled in the study. The inactivated hepatitis A vaccine was produced by Tangshan Biogenetic Company. The dosage of the vaccine was 1000 U/Dosage and 500 U/Dosage. The vaccination schedule was six month apart for two injections. The serum anti-HAV level was detected with EIA at one month after first injection and at one and six month after the booster injection, respectively., Results: The anti-HAV appeared in all the children. One month after the booster injection, the serum anti-HAV level in children vaccinated 500 U/Dosage was 4684.9 mIU and 4535.6 mIU, respectively and in the children vaccinated 1000 U/Dosage, 5399.8 mIU and 7347.1 mIU, respectively. The anti-HAV level was not statistically different between the two groups of children. There was no adverse reaction after the vaccination. The anti-HAV level was still high one year after first injection., Conclusions: The data indicated that the safety and immunogenicity of the domestic inactivated hepatitis A vaccine were excellent in both groups of children.

Background: To evaluate the safety and immunogenicity of a new inactivated hepatitis A virus (HAV) vaccine., Methods: In a randomized controlled trail thirty-one HAV-seronegative adults were enrolled and randomly assigned to either study group or control group. Subjects in the study group were given 1000 units of the new inactivated HAV vaccine, with a booster at 3 months. Subjects in the control group were given 720 ELISA units Havrix, produced by SmithKline Beecham Biologicals, with a subsequent dose at 3 months. Local and systematic reactions and serum response to the vaccines were compared between the two groups., Results: Mild local reactions were noted in one subject from the study group and two from the control group after primary vaccination. Mild systematic reactions were reported in two subjects from each group after primary vaccination and in one subject from the study group after booster vaccination. Seroconversion rates were 94%, 100%, and 100% in the study group at 1, 3, and 4 (1 month after booster) month, respectively. The corresponding figures were 73%, 80% and 100% in the control group. Geometric mean antibody titers were 139.2 mIU/ml, 137.7 mIU/ml, and 1 066.7 mIU/ml at 1, 3, and 4 months,respectively, in the study group,and 104.3 mIU/ml, 111.3 mIU/ml, and 760.7 mIU/ml in the control group., Conclusions: The new inactivated hepatitis A vaccine was safe and highly immunogenic.

Objective: To compare the antibody level of vaccine group and control group in a randomized, controlled trial of type B inactivated vaccine against hemorrhagic fever with renal syndrome(HFRS) in Jiande County of Zhejiang Province and to find out if there is enhancement of subclinical infection about type B inactivated vaccine against HFRS., Methods: The number of sera collected (July 1994-July 1998) in vaccine group immunized type B inactivated vaccine against HFRS and control group were 305 and 283 persons in Jiande County respectively, and indirect immunofluorescent antibody method(IFAT) was used for testing the titer of HFRS IgG in sera. The cut-off values were determined on IFA titer of the second sera in control group with positive and negative IFA before vaccine was given respectively, and the subclinical infection of positive and negative IFA of the first sera in vaccine group was evaluated., Results: When taking different cut-off values of subclinical infection, there were no statistical differences in HFRS IFA positive rates between vaccine group and control group of positive IFA in the first sera. In vaccine group and control group of negative IFA before vaccine given, also the IFA positive rates were not statistically different in these groups. There were no statistical differences of IFA GMT and IFA sero-negative rate between vaccine group and control group., Conclusions: The investigation showed there was no statistical difference in antibody level between vaccine group and control group, so there could not be enhancement of subclinical infection of vaccine group receiving type B inactivated vaccine against HFRS.

Objective: This study was carried out to assess the long-term persistence of antibodies against hepatitis A in different vaccine dosage groups., Methods: One hundred and sixty-six susceptibles aged form 6 to 8 years old were selected in Zhengding county, and were divided into 4 different dose groups. Each group received 10(6.17)TCID(50), 10(6.52)TCID(50), 10(6.83)TCID(50) of attenuated hepatitis A vaccine or 10(6.83)TCID(50) of the same vaccine but treated with 60 degrees C for 3 hours. All subjects were bled at month 3, 12, 24, 36 and 48. All serum specimens were tested for antibodies to HAV using Abbott-IMx mEIA reagent. Part of the tested negative serum specimens were retested by neutralization assay for 10(6.52)TCID(50) and 10(6.83)TCID(50) dosage groups at 4 years after vaccination., Results: The seroconversion rate and GMT 3 months after vaccination in each dosage group showed a significant dose-response relationship. Antibody levels reached the peak at month 3 in each group but declined dramatically within one year and the decline slowed down thereafter. The serocoversion rate and GMT in 10(6.83)TCID(50) dose group 4 years after vaccination was significant higher than those of other dosage groups. Positive rates of neutralizing antibodies in B and C dosage group were 60.0% and 83.3% respectively., Conclusion: The immunogenicity and long-term persistence were related to the attenuated hepatitis A vaccine titer. The vaccine, whose titer was 10(6.83)TCID(50), had good immunogenicity and long-term persistence. Booster dose was not needed within short time after initial vaccination.

Objective: Safety and immunogenicity of inactivated bivalent EHF vaccine in humans were evaluated in the epidemic area of Zhejiang province, China., Methods: Susceptible persons with negative anti-EHF were selected in Jiande county, Zhejiang province to receive 3 doses of inactivated bivalent EHF vaccine at 0, 7, 28 days. A booster injection was given one year after the primary immunization. Antibody responses were measured in human volunteers by IFA and MCPENT. Local and general reactions were recorded within 72 hours after each vaccination by physicians., Results: Two weeks after the primary vaccination, 99.04% of the subjects developed significant hantavirus antibody titre measured by IFA which had a 37.34% drop one year after the primary vaccination. Seroconversion rate increased to 100% two weeks after the booster dose. Neutralising antibody titres paralleled this trend with 100% of vaccine recipients producing neutralising antibody two weeks after the primary doses. However, it dropped to 80% one year after the primary vaccination. One hundred percent of the vaccine recipients started to respond two weeks after boosting. The geometric mean titre (GMT) of neutralising antibody against 76 - 118 and UR were 18.27 +/- 2.21 and 12.47 +/- 2.16 respectively after the primary injections, but it increased to 37.09 +/- 2.24 and 32.61 +/- 2.05 respectively after the secondary immunization. General and local reaction rates were 0.46% and 1.98%, with no severe side effects observed in the vaccinees., Conclusion: The vaccine was well tolerated and could induce good humoral immune response.

Objectives: To observe the changes in serum antibody level after mass immunization with vaccine against hemorrhagic fever with renal syndrome (HFRS) and to evaluate its efficacy and effectiveness in the prevalent areas., Methods: Healthy people aged 16 to 60 years in the villages were recruited as study subjects, excluding those suffered from HFRS previously, going out for more than nine months and those with contraindications, and were randomly allocated into immunization and control groups with 10,460 and 16,159 persons, respectively. Specific IgG antibody was determined with indirect immunofluorescent assay (IFA) and neutralizing antibody (NA) was determined with micro CPE method., Results: Two weeks after the full-course immunization, sero-conversion rate for IFA reached 100% in those sero-negative before immunization, with a 95% confidence interval of 96.3 - 100.0%, and that for NA 44.4%, with a 95% CI of 22.0% - 69.0%. Geometric mean titer (GMT) were 72.1 and 4.6 for IFA and NA, respectively. Booster immunization was provided for them one year later. Positivity of IFA and NA was 28.6%, 83.3%, 75.0%, 53.1%, 22.6% and 14.8%, 55.6%, 35.0%, 31.3%, 26.0%, before booster immunization, two weeks, one year, one and a half years, two years after booster immunization, respectively., Conclusion: HFRS vaccine had good immunogenicity, but its duration of serum antibody sustenance was relatively short.

Objective: To observe the safety and the preventive effects of three kinds of vaccines as Mongolian gerbils kidney vaccine, mouse brains vaccine and hamster kidney vaccine inoculated 5 years ago., Methods: Field study and laboratory tests were carried out by random grouping and IFAT, MCPENT, ELISA, HI tests., Results: The antibody-dependent enhancement did not appear in all individuals who received vaccines after four or five years. The seroconversion rates of MCPENT were 8.97%, 11.76% and 18.75% while the seroconversion rates of IFAT were 20.73%, 30.22% and 23.40% respectively for Mongolian gerbils kidney vaccine, mouse brains vaccine and hamster kidney vaccine. The protection rates were 100% for all three kinds of inactive vaccines which showed good epidemiological efficacy., Conclusion: The vaccines can protect clinical infection of EHF effectively after four or five years of the initial vaccination.

Objective: To evaluate three vaccination schedules of inactivated hepatitis A vaccine in rhesus monkeys (Macaca Mulatta)., Methods: Seventeen rhesus monkeys were divided randomly into four groups. The first group of five monkeys was immunized with vaccination schedule 1 (one immunization at week 0); The second group of five monkeys was immunized with vaccination schedule 2 (first injection at week 0, and booster one at week 4); the third group of five monkeys was immunized with vaccination schedule 3 (first injection at week 0, and booster one at week 24); and the fourth group of two monkeys with MEM as control. Rhesus monkeys were inoculated by intramuscular injections to detect the ALT (alanine aminotransferase), liver pathology and anti-HAV at different time., Results: During the 52-week observation, no abnormal elevation of ALT or liver pathology appeared. The IgG response for vaccination schedule 1 reached the highest level (13 219 mIU/ml), and decreased gradually to 2 056 mIU/ml at week 52. After booster immunization at week 4, the IgG response for vaccination schedule 2 was 13 863 mIU/ml at week 12, and decreased to 6 285 mIU/ml. The highest level of IgG (40 638 mIU/ml) for vaccination schedule 3 appeared at week 28 after booster injection at week 24. Further more, at week 52 the IgG level for vaccination schedule 3 was also the highest among the three vaccination schedules., Conclusions: The inactivated hepatitis A vaccine is safe and well immunogenic. The vaccination schedule 3 showed the best immune response among the three vaccination schedules.

Objectives: To investigate the safety and immunogenicity of AVAXIM in children and adults., Methods: One hundred and twenty-one children aged 6 - 12 years and 108 adults with negative HAV antibody, were inoculated by 0, 6 month procedure with inactivated HAV vaccine produced by Pasteur Merieux Connaught (AVAXIM 160 antigen unit)., Results: The positive rates of anti-HAV IgG among children group and adult group were 98.15% and 94.17% respectively after one month of first inoculation, and became 100% and 97.22% after one month of second inoculation. The antibody positive rate was higher in children than in adults, but did not show statistical significance (P < 0.05). The side effects of AVAXIM inoculation were mild, mainly local pain with occurrences 1.7% - 2.8% in both groups. No serious systemic and local reactions were noticed., Conclusion: AVAXIM had good safety and immunogenicity, seen not only in adults, but also in children.

Objective: To study the immunology effects of live attenuated hepatitis A vaccine in different doses and schedules groups, and compare with inactivated hepatitis A vaccine (Havrix, Smithkline)., Methods: 318 susceptible children were enrolled in Guangxi and Hebei province. These subjects were divided into six groups. Each group was vaccinated with either inactivated vaccine or different doses and schedules of live attenuated vaccine. Serum specimens were collected and tested for anti-HAV antibody at different time after the vaccination., Results: GMT of each group arrived at the peak 1 months after re-vaccination, then declined, and GMT of 6 months after booster dose was still significantly higher than that after primary immunization. Sero-conversion rates in all groups reached 100% after a booster dose, and kept at 6 months after booster dose., Conclusions: A booster dose of live attenuated vaccine can induce secondary immune response well. The immunology effects after booster dose are comparable with inactivated vaccine and it should be useful to the immune persistence.

Objective: To study the immunologic effect of live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50)) after booster and to compare with the results of 1 dose live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50))., Methods: 42 susceptibles with negative anti - HAV were selected in Zhengding, Hebei province. Each subject received 3 doses live attenuated hepatitis A vaccine at 0, 2, 6 months and was bled at 1, 2, 6, 7, 9, 12 months after vaccination., Results: The seroconversion rate at 1 month after the first dose was 81.4% and reached 100% after the second dose. GMT arrived the peak 2,739 mIU/ml at one month after the third dose, before stared declining. The seroconversion rate kept 100% at 12 months after the first dose, but GMT decreased to 979 mIU/ml., Conclusion: The first dose worked as the base of boostering. A booster dose of live attenuated hepatitis A vaccine could induce secondary immune response well. The immunologic effect after booster dose could match the effect with inactivated vaccine and was better than the results of 1 dose live attenuated hepatitis A vaccine. The program seemed to be useful to the protective effect and the immuno - persistence.

Objective: To study side effects and effectiveness of bivalent inactivated vaccine against hemorrhagic fever with renal syndrome in population of a randomized controlled field trial., Methods: Serum indirect immunofluorescent antibody in 167 persons and neutralization antibody (types I and II) in 69 persons, who received three-dose vaccine, were determined two weeks after immunization, and side effects in 657 vaccinees were observed within 72 houses after immunization., Results: Serum positive conversion rate of indirect immunofluorescent antibody was 99.04% (166/167) with GMT of 24.51 +/- 2.06. Serum positive conversion rate of neutralization antibody was 100% (69/69), 91.30% (63/69) for types I and 88.41% (61/69) for type II, respectively. GMTs for type I and II neutralization antibody were 18.27 +/- 2.21 and 12.47 +/- 2.16, respectively. Side effects at local site vaccinated of the body and temperature rising could be seen in 1.48% and 0.36% of the vaccinees, respectively. No severe side effect and abnormal reaction was found in vaccinees on the field., Conclusion: Immune response to bivalent inactivated vaccine against hemorrhagic fever with renal syndrome was satisfactory with slight side effect.

Objective: To develop a kind of new Japanese Encephalitis (JE) vaccine prepared on Vero cells., Methods: A JE attenuated virus strain SA14-14-2 was adapted on Vero cells for preparation of purified inactivated vaccine. Comparison of the growth curves of SA14-14-2 in roller bottle and in spinner flask was made. After the virus inoculation and absorption on Vero cells for 2 hours, cultures were replaced with serum-free MEM, the culture supernatants were harvested on day 2,4,6 after inoculation. The virus fluids were pooled, concentrated by 8% PEG, and purified on 15%-60% sucrose density gradients. The purified virus was inactivated with 0.02% formalin., Results: It showed that virus titer was higher and maintained longer in roller bottle. Mice vaccinated twicely with 0.5 microgram dose of the purified inactivated vaccine induced neutralizing antibody titers equal to that of the mice vaccinated with primary hamster kidney inactivated vaccine., Conclusion: This Vero cell prepared purified and inactivated JE vaccine made by SA14-14-2 strain could be used for human as a kind of new JE vaccine.

319 infants aged 5-18 months were divided in to 2 groups and immunized with Japanese encephalitis virus inactivated vaccine and live attenuated vaccine respectively. Under the detection of serum antibody, a 3.76% serum antibody positive rate was revealed before the immunization. However, after the basic immunization the serum positive rates of the two vaccines reached 59.56% and 56.08% respectively but still under the protective level. The infants were then given booster injection one year later. The serum positive rates reached 94.62% and 98.21% respectively 1 month later. When six months after the booster immunization, the positive rates were 72.34% and 94.74% respectively. According to the results, the following immunization order was recommend. For inactivated vaccine: 2 injections are given with an interval of 7-10 days for basic immunization and booster immunization be given in the second and third years. For live attenuated vaccine: one injection is given for basic immunization then booster dose be given in the second year and 4-5 years later.

Kinetics of cellular immune responses was studied in C57BL/6 mice immunized with irradiation-attenuated vaccine, cryopreserved and irradiated vaccine or frozen-thawn vaccine. The results and analysis of correlation between cellular responses and resistance showed that cellular immune responses played an important role in the protective immunity against Schistosoma japonicum.