Résumé
To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.
Résumé
Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.
Sujets)
Humains , Plan de recherche , Recherche biomédicale , Immunisation , Vaccins/usage thérapeutiqueRésumé
Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.
Sujets)
Humains , Plan de recherche , Recherche biomédicale , Immunisation , Vaccins/usage thérapeutiqueRésumé
With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.
Sujets)
Humains , COVID-19 , Vaccins contre la COVID-19 , SARS-CoV-2 , VaccinsRésumé
BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Sujets)
Adulte , Humains , COVID-19 , Vaccins contre la COVID-19 , Méthode en double aveugle , SARS-CoV-2 , Vaccins inactivés/effets indésirablesRésumé
To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49 (95: 40-57). Subgroup analysis found that the protection rate of LAIV was 35 against influenza A (H1N1) pdm09 (95: 5-56), 35 against influenza A (H3N2) (95: 21-46), and 71 against influenza B (95: 55-82). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56 (95: 48-63) and 44 (95: 27-57), respectively. The protection rates of LAIV in Europe and North America were 65 (95: 47-77) and 46 (95: 36-55), respectively. LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.
Résumé
Objective To establish a dynamic model of hand foot and mouth disease in Jiangsu Province, analyze the epidemic of hand foot and mouth disease in Jiangsu, predict the trend of this disease and simulate the effect of EV71 vaccination on the control of hand foot and mouth disease caused by EV71. Methods A compartmental model of hand foot and mouth disease was constructed.A group of differential equations was established. The incidence data of hand foot and mouth disease was used to fit the model and calculate the basic reproduction number of this disease in Jiangsu. Then, vaccination was added to the model and the incidence of hand foot and mouth disease under different vaccination coverage rates was simulated. Results The basic reproduction numbers of hand foot and mouth disease in Jiangsu between 2013 and 2016 were 1.31 (IQR:0.99-1.48), 1.37 (IQR:0.97-1.52), 1.34 (IQR:1.00-1.61) and 1.38 (IQR:1.00-1.76) , respectively. With the increase of immunization coverage of EV71 vaccine, the cases of hand foot and mouth disease caused by EV71 decreased accordingly. When the annual immunization rate of EV71 vaccine was maintained at a high level (75%), the annual incidence of hand foot and mouth disease caused by EV71 after 5 years reduced to 10% of that in the same year when there was no vaccination. Conclusions The epidemic trend of hand foot and mouth disease in Jiangsu is stable from 2013 to 2016. Vaccination plays an important role in controlling hand foot and mouth disease caused by EV71.
Résumé
During the past 70 years since the founding of New China, Chinese public health especially the prevention and control of infectious diseases have made remarkable achievements, which benefited from the vaccination. This study is to summarize the progress of immunization and vaccines, the achievements and contributions of vaccines including polio vaccine, hepatitis B vaccine, diphtheria, tetanus and acellular pertussis combined vaccine, measles vaccine and hepatitis A vaccine to the prevention and control of infectious diseases in China in the past 70 years and to review the research and development of innovative vaccines in China in recent years, which may provide clues for the development of the expanded programe on immunization in China in the future.
Résumé
Herpes zoster (HZ) is more common in middle-aged and elderly people, and is caused by varicella-zoster virus (VZV) that is latent in sensory ganglia. In recent years, due to various reasons, especially the aging of China's population has become more serious, the incidence of HZ in China has risen sharply. Although HZ is self-limited, its complications will still reduce the quality of life of patients and increase the economic burden of patients' families and society. In order to reduce the incidence and improve the quality of life of the elderly in their later years, the development of safe and effective HZ vaccine may be an important and effective measure. This article aims to make a brief review of the progress in research for clinical trials of HZ vaccines, so as to provide a reference for the use of HZ vaccine and the prevention and control of HZ disease in China.
Résumé
Objective To compare the antibody response induced by primary immunization with 5 μ g and 10 μ g hepatitis B vaccine made by recombinant DNA techniques among the newborns.Methods Healthy infants who had completed primary immunization with 5 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Saccharomyces (Hep-SC) or 10 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) were included in the study.Kids under study were 7-12 months of age and had been on 0-1-6 schedule.Standardized questionnaire was used and blood samples were collected.The titer of antibody to hepatitis B surface antigen (anti-HBs) was detected by Chemiluminescence Microparticle Imunoassay (CMIA).If anti-HBs happened to be under 10 mIU/ml,HBV DNA was further detected by nested-PCR to distinguish occult hepatitis B virus infection.Sero-conversion rate and titer of anti-HBs were compared between the two kinds of hepatitis B vaccines.Multivariate analysis was used to find the relationship between the kind of hepatitis B vaccine as well as the antibody response after debugging the other influencing factors including month-age,gender,birth-weight,premature birth and mother' s HBsAg status.Results 8947 infants vaccinated with 5 μg HepB-SC and 4576 infants vaccinated with 10 μg HepB-HP were investigated.In the 5 μg group,the rates of non-,low-,normal- and high-response were 1.88%,15.18%,61.42% and 21.52% respectively.In the 10 μg group,the corresponding rates were 0.15%,2.16%,29.42% and 68.26% respectively.The non-,low-,normal-response rates were all higher in 5 μg group than in 10 μg group (P<0.01),while the high-response rate was much higher in 10 μg group than in 5 μ g group (P<0.01).The geometric mean concentration (GMC) of anti-HBs were 354.81 mIU/ml (95% CI:338.84-363.08 mIU/ml) and 1778.28 mIU/ml (95%CI:1698.24-1819.70 mIU/ml) in the 5 μg group and 10 μg group respectively.The GMC was statistically higher in the 10 μg group than in the 5 μg group (P<0.001).The seroconversion rate and GMC were significantly different between the two groups even after debugging the other influencing factors.Conclusion Better anti-HBs response could be achieved by primary immunization with 10 μg HepB-HP than with 5 μg HepB-SC among newborns.
Résumé
Objective To compare the antibody response between preterm and full-term infants after primary immunization of hepatitis B vaccine (HepB).Methods Infants who were aged 7-12 months and had completed primary immunization with 5 μg HepB made by recombinant dexyribonucleic acid techniques in saccharomyces cerevisiae (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) on 0-1-6 schedule were investigated in four provinces (municipality) including Beijing,Shandong,Jiangsu and Guangxi of China.Among them,all preterm infants were selected to form the preterm group and the 1:1 matching full-term infants with the same month-age,gender and residence were randomly selected to form the full-term group.Their HepB history was determined by immunization certificate and all of their parents were interviewed with standard questionnaire to get their birth information.Blood samples were obtained from all anticipants and were tested for Anti-HBs by chemiluminescence microparticle immuno-assay (CMIA).Results Total anticipants were 648 pairs of infants.The rates of non-response,low-response,normal-response and high-response after the primary immunization were 1.39%,8.64%,45.83% and 44.14% in the preterm group,respectively.The corresponding rates were 1.08%,9.26%,44.91% and 44.75% in the full-term group.The above four rates did not show significant differences between the two groups (P>0.05).The geometric mean concentrations (GMC) of anti-HBs in the pre-term and full-term group were 755.14 and 799.47 mIU/ml respectively.There was no significantly difference in the GMCs between the two groups (P>0.05).Results from multivariable conditional logistic analysis showed that preterm was not an influencing factor to the antibody response after HepB primary immunization among newborns even after debugging the other influencing factors.Conclusion The autibody response after HepB primary immunization were similar among the preterm and full-term infants.The preterm newborns could be immunized under the same HepB immunization strategy.
Résumé
<p><b>OBJECTIVE</b>To analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (HFMD) seen in Jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.</p><p><b>METHODS</b>Based on the requirement of supervision program of HFMD, surveillance and report were done according to National Disease Supervision Information Management System. Descriptive epidemiological method, performed between 2008 and 2010, was used to analyze the time, region and population distribution and results of etiologic analysis of HFMD. Nucleic acid of enterovirus (EV) genome was detected by real-time RT-PCR.</p><p><b>RESULTS</b>The average incidence rate of HFMD was 86.70 per million between 2008 and 2010, the peak incidence occurred in April to July. There were significant differences among the incidence in different districts (P<0.05), and the highest incidence was seen in the densely inhabited southern areas of Jiangsu province. Most of the cases were infants and children aged less than 5 years. The number of male cases (2008: 17,008, 2009: 48 768, 2010: 50,231) was much larger than that of the female cases 2008: 9662, 2009: 29 151, 2010: 30,655. The HFMD cases with mild symptoms were caused mainly by enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) and there was difference among different years. The severe HFMD cases and deaths were mainly caused by EV71 infection.</p><p><b>CONCLUSIONS</b>The epidemiologic characteristics of HFMD in Jiangsu province from 2008 to 2010 had close relationship with season, population and region. The mild cases of HFMD were mainly infected with EV71 and Cox A16. However, EV71 illness seemed to be more severe and had significantly greater frequency of serious complications and fatality than the illness caused by Cox A16.</p>
Sujets)
Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Chine , Épidémiologie , Épidémies de maladies , Entérovirus humain A , Virulence , Syndrome mains-pieds-bouche , Épidémiologie , VirologieRésumé
Globally, about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection. A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples. The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions. This phase I trial (NCT00549900) assessed the safety, tolerability, and immunogenicity of the vaccine in Chinese. Thirty healthy Chinese females, aged 15 to 45 years with a median age of 29.5 years, received three doses of Cervarix in Months 0, 1, and 6. Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination. Serious adverse events, new onset of chronic diseases, and other medically significant conditions were recorded throughout this trial. As an exploratory objective, HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7. Pain at the injection site was the most frequently reported local symptom. Two subjects reported medically significant adverse events. Both cases were assessed as unrelated to vaccination by the investigator. In Month 7, 100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers. HPV-16/18 AS04-adjuvanted vaccine, evaluated for the first time in Chinese females, was generally well tolerated and immunogenic, as previously shown in global studies.
Sujets)
Adolescent , Adulte , Femelle , Humains , Adulte d'âge moyen , Jeune adulte , Adjuvants immunologiques , Anticorps antiviraux , Sang , Asiatiques , Chine , Papillomavirus humain de type 16 , Allergie et immunologie , Papillomavirus humain de type 18 , Allergie et immunologie , Infections à papillomavirus , Allergie et immunologie , Virologie , Vaccins contre les papillomavirus , Utilisations thérapeutiques , Tumeurs du col de l'utérus , Allergie et immunologie , VirologieRésumé
Objective To investigate the status of infection and distribution of rabies virus (RV) in different epidemic areas in China. Methods Brain specimens from animals and suspected patients were collected at the districts of high-, medium- and low incidence rates of human rabies and detected by both direct Immunofluorescence assay (DFA) and RT-PCR. Results 254 of 3007 specimens of dog brains showed RV positive by DFA (positive rate of 8.4% ). Among these 254 samples, 78 showed positive (positive rate of 30.7% ) by RT-PCR. 93 specimens from dogs and cats that had attacked human beings, 63 of them showed positive by DFA (positive rate of 67.7%) and all of them were also positive by RT-PCR. In addition, RV could also be detected in Apodemus agrarius,ferret badger, and suspected patients specimens from the districts under survey. There was no statistical difference between the infection rates of RV in different provinces and regions with different incidence of rabies. Conclusion There might be a relatively high infection rate of RV among the domestic dogs/cats in the endemic areas in China. Wild animals might have been infected with RV in the districts under survey.
Résumé
<p><b>BACKGROUND</b>Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently.</p><p><b>THE AIMS OF OUR STUDY WERE</b>to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.</p><p><b>METHODS</b>Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.</p><p><b>RESULTS</b>Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P < 0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.</p><p><b>CONCLUSIONS</b>The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.</p>
Sujets)
Femelle , Humains , Nourrisson , Nouveau-né , Anticorps neutralisants , Sang , Allergie et immunologie , Cellules cultivées , Enterovirus , Allergie et immunologie , Entérovirus humain A , Allergie et immunologie , Syndrome mains-pieds-bouche , Allergie et immunologie , VirologieRésumé
Objective To determine the epidemiological features of hand-foot-and-mouth disease (HFMD) outbreaks and the genetic characteristics of enterovirus type 71 (EV71) isolates from patients in Lianyungang, Jiangsu province in May, 2008. Methods Epidemiological, microbiological, cellular and molecular methods were performed to investigate pathogens and to describe the homogeneity of isolated strains. Results 21 cases were reported in this HFMD outbreak with the attack rate as 20.0%. 3 EV71 virus strains were isolated from 10 stool samples. The nucleotide and amino acid homogeneity of these 3 Jiangsu strain with Anhui Fuyang strains were 97.9%-100.0% and 99.7%-100.0%, respectively. These 4 Jiangsu strains were within genotype C sub-geno group C4 in phylogenetic tree. Data from the follow-up study showed that shedding of EV71 and Coxsackie A 16 virus (CA 16) in the latent period appeared in the outbreak of HFMD. Human beings could be infected by both EV71 virus and CA16 at the same time and could also carry the two viruses. We also discovered that EV71 virus could be expelled out of the human body through stool in the fast week and last for 10 weeks. Conclusion The recently identified EV71 isolates from this HFMD outbreak belonged to sub-geno group CA. Facts as: the release of viruses in the latent period, co-infection or coexisting of two viruses at the same time and super long period of expulsion of toxin exist in EV71 and CA16 did exist.
Résumé
Objective To study the kinetics of immune response in mice and human immunized with rHB vaccine or rHBsAg derived from yeast cells(Hansenula polymorpha).Methods With different doses,the level of IFN-γ secreted by spleen mononuclear cells(MNC)including CD8+T cells by MACs of mice were detected by enzyme-linked immunospot(ELISPOT)methods after stimulation in vitro with HBsAg MHC class Ⅰ peptide S28-39,respectively.At serial time points.the immunized mice were detected for IFN-γ by ELISPOT as above and for the lymphocytotoxicity test(CTL)by specific lysis assay.The levels of IFN-γ,IL-2,IL-5 and anti-HBs in mice induced by rHB vaccine were detected after single or three doses.Four adults were vaccinated with rHB vaccine according to 0,1 and 2 month schedule.The peripheral blood mononuclear cells(PBMCs)were collected at the 3,8,21,34 and 65 days after the first dose.The CD8+T cells with high purity obtained by sorting from PBMcs were stimulated with rHBsAg or HBsAg peptides.The SFC of IFN-γ,IL-2 and IL-4 of CD4+ and CD8+ T cells were determined by ELISPOT.Results The cytokine of IFN-γ became detectable on day 7 and its peak value appeared on day 14 by ELISPOT.The CTL was detected on day 7 and the maximum lysis of CTL appeared on day 28.The cellular immune response of IFN-γ of MNCs were significantly correlated with the doses vaccinated from 1 μg to 8 μg(Υpositive rates=0.951,Ppositive rates=0.049<0.05;rSFC=0.996,PSFC=0.000<0.05).IFN-γSFC of CD8+T cells were significantly associated with the doses from 1 μg to 4 μg(Υ=0.999,P=0.025<0.05).The HBsAg specific cellular immune and humoral responses of mice immunized with three doses were significantly higher than that with a single dose(P<0.05).The characteristics of IFN-γ,IL-2 and IL-4 of CD4+ and CD8+ T cells were variable between individuals immunized with the same rHB vaccine.The level of IL-2 and IL-4 of responders were significantly related to the titer of anti-HBs.Conclusion Data from this study showed the kinesis of cellular immunity in mice and adults vaccinated with rHBsAg or rHB vaccine respectively.and the characteristics of cellular immune response in adults induced by the vaccine.Our data provided the basis of standardizing the analysis of cellular immune response to rHB vaccine.
Résumé
For epidemiological investigation of the rabies virus carrier rates of domestic dogs, cats and wild animals like rodent animals and bats,three kinds of regions where rabies had higher incidence (Hunan and Guizhou Provinces), lower incidence (Jiangsu Province, Wuhan City) and provisionally rabies-free (Shenyang City) were selected. Then the antigenic types, the genovariation of the isolaled viruses and the currently vaccine matching of the virus strains were analyzed. The results showed that in China the principal host of rabies is dog,the total virus carrier rate of the captured dogs was 2.56%, and the highest positive isolation rate was 20.0% in some monitoring site. However,there was no evidence about the rabies virus carrier rate in rodent animals,bats or other wild animals. The rabies vaccines which prepared from aG and CTN strains have already been produced successfully in China. The research showed that the nucleotide sequences of the newly isolated viruses were more similar with the glycoprotein gene of CTN strain. In order to evaluate the safety and the efficacy of the vaccines currently used, two groups (50 people each) were injected with vaccine of aG strain and CTN strain respectively in five surveillance points. The neutralizing antibody tested were 0.49 IU/mL-0.52 IU/mL and 6.7 IU/mL-7.53 IU/mL after the 7 and the 14 days of vaccine injection respectively. In addition, the rates of antibody positive seroconversion were 45.1%-47.9% and 100% respectively, and there was no moderate or severe adverse reactions observed. These data showed the vaccines have satisfactory effect on safety and protection.
Sujets)
Animaux , Chats , Chiens , Anticorps antiviraux , Sang , État de porteur sain , Épidémiologie , Virologie , Chlorocebus aethiops , Virologie , Test ELISA , Technique d'immunofluorescence , Vaccins antirabiques , Allergie et immunologie , Virus de la rage , Classification , Génétique , Cellules VeroRésumé
<p><b>OBJECTIVE</b>To study how hepatitis B virus(HBV) 'a' determinant hotpoint mutations were influecing the hepatitis B vaccine efficacy.</p><p><b>METHODS</b>Primers were designed in HBV conservative region, and the degenerate probes for detecting 16 'a' determinant hotpoint mutations were developed for gene chips. Sensitivity and specificity of the gene chips were evaluated by clone sequencing. Sera of 47 pairs of mothers and infants with immune failure and 323 mothers of children with immune protection of HB vaccine were detected by the gene chips.</p><p><b>RESULTS</b>Result from clone sequencing demonstrated that the gene chips were specific for the detection of 'a' determinant hotpoint mutations. The wild type of HBV was still dominant, with the prevalence of 78.66%, and the mutation frequencies of 126A, 145R, 126S-1, 126S-2, 129H, 144A, and 129R were 11.27%, 5.76%, 5.28%, 4.56%, 1.20%, 0.72% and 0.24%, respectively. The prevalence of 126A mutation was significantly higher than that of other mutations(P < 0.01). No significant differences were found in mother-infant transmission rates of 126A, 126S-1, 126S-2 and 145R variants.</p><p><b>CONCLUSION</b>The currently available hepatitis B vaccine could block mother-infant transmission of 126A, 126S and 145R variants. It appears that there is no need to develop a new hepatitis B vaccine against 126 and 145 variants at present, but the consistent epidemiological surveillance on HBV mutants should be carried out.</p>
Sujets)
Adulte , Femelle , Humains , Nouveau-né , Grossesse , Génotype , Hépatite B , Vaccins anti-hépatite B , Allergie et immunologie , Virus de l'hépatite B , Génétique , Allergie et immunologie , Transmission verticale de maladie infectieuse , Mutation , Séquençage par oligonucléotides en batterie , Complications infectieuses de la grossesse , VirologieRésumé
<p><b>OBJECTIVE</b>To evaluate the kinesis of cellular immunity in adults who were vaccinated with yeast recombinant hepatitis B(rHB) vaccine and the correlation between cellular and humoral immune responses induced by the vaccine.</p><p><b>METHODS</b>Eight adults were vaccinated with rHB vaccine according to 0, 1,2 month schedule. The peripheral blood mononuclear cells(PBMCs) were collected at the 3, 8, 21, 34 and 65 days after the first dose. The high purity of CD4+ and CD8+ T cells obtained by sorting from PBMCs were restimulated with recombinant hepatitis B surface antigens (rHBsAg) or peptides. The spot forming cell (SFC) of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells were detected by enzyme-linked immunospot (ELISPOT).</p><p><b>RESULTS</b>The characteristics of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells appeared different after immunization with rHB vaccine. IFN-gamma of CD8+ and CD4+ T cells could be detected early with stable SFC, while the IL-2 and IL-4 of CD4+ T cells appeared late but increased after the second and third dose of vaccination. The positive rate of IL-4 of CD4+ T cells were significantly correlated with the positive rate of anti-HBs, while the SFCs of IL-4 and IL-2 of CD4+ T cells were also significantly related to the titers of anti-FIBs.</p><p><b>CONCLUSION</b>IFN-gamma could be detected early after rHB vaccination in adults, and the positive rates of IL-4 and IL-2 were correlated with that of anti-HBs.</p>