肾综合征出血热病人病后中和抗体调查

对山东省１９９２～１９９７年肾综合征出血热（ＨＦＲＳ）疫区显性感染及隐性感染人群血清ＩｇＧ抗体与中和抗体进行检测,提示随病后时间延长ＩｇＧ抗体滴度逐年下降,有的从血清中消失。而中和抗体持久存留,是ＨＦＲＳ病后机体免疫力的标志,报告如下。１　材料与方法１－１　血清标本　根据既往疫情资料,选择博山、张店、临淄、胶县、胶南等区县,采集显性感染人群血清１０７份;隐性感染人群血清２０份;非疫区健康人群血清８４份。１－２　标准毒株　姬鼠型毒株７６～１１８;家鼠型毒株Ｒ２２。１－３　实验动物　昆明系小鼠。１－…     

非洲撒哈拉以南地区人类的黑猩猩腺病毒抗体

用来自美国、泰国以及非洲撒哈拉以南地区的人类血清和黑猩猩血清，检测出了针对三种黑猩猩腺病毒的中和抗体。这些抗体在非洲撒哈拉以南地区居民血清中比居住在美国和泰国的人更常见。结果表明黑猩猩腺病毒存在种间交叉传播。     

狂犬病动物抗体水平检测和监测

检测人和动物体内狂犬病抗体的主要目的有三个方面,第一,对暴露前预防免疫的人或动物进行抗体监测,确定人的预防免疫效果和动物的免疫水平及免疫覆盖率;第二,对暴露后免疫治疗的人体内的中和抗体进行检测,以确定暴露后治疗效果;第三,对狂犬病疑似患者或患畜,通过测定患病早期和     

狂犬病疫苗接种人群中狂犬病病毒中和抗体水平分析

目的 通过分析狂犬病疫苗接种人群中狂犬病病毒RABV中和抗体特征,为狂犬病防控提供依据。方法 收集2019-2020年杭州市职业病防治院犬伤后暴露预防接种门诊抗体检测者信息,经筛选后确定157例RABV中和抗体检测者作为研究对象,采用快速荧光灶抑制试验检测狂犬病毒中和抗体,利用横断面研究方法对狂犬病毒中和抗体水平进行人群特征分析。结果 研究对象中,初种者98人,复种者59人,复种者中2-1-1程序比5针法产生的抗体水平更高,其余特征均无统计学差异(P>0.05)。除1例初种者中和抗体效价低于0.5 IU/mL,其余检测者中和抗体效价均高于0.5 IU/mL。狂犬病毒中和抗体水平时间趋势分析显示,狂犬病毒中和抗体水平与时间呈负相关,回归方程为(F=4.974,P=0.031),标准化回归系数为-0.322(t=-2.230,P=0.031)。结论 复种者狂犬病毒中和抗体水平与免疫程序有关,2-1-1程序对人体再次免疫应答的效果优于5针法。接种疫苗2年后部分个体出现失保护状态,再次暴露有必要全程接种狂犬病疫苗。     

RFFIT和MNT检测狂犬病毒中和抗体的比较研究

目的 对RFFIT和MNT两种方法检测抗狂犬病毒中和抗体的相关性,敏感性和重复性进行比较.方法 用MNT和RFFIT两种方法来检测已免疫的人血清52份,未免疫的人血清40份.结果 显示这两种方法检测已免疫血清的一致性是88.5%,其相关性是r=0.886,MNT的敏感性和特异性分别是84.9%,100%,RFFIT的灵敏度和特异性分别是100%,89.0%.MNT和RFFIT重复检测一个样品的变异系数(CV)分别是62.3%、13.3%.结论 RFFIT与MNT的相关性较好,RFFIT的灵敏度和重复性均比MNT好,因此,RFFIT在大多数需要检测RV中和抗体的情况下可替代MNT.     

心脏病患者血清Coxsackie B组病毒中和抗体的调查

44例不明原因早搏患者的Coxsackie B组病毒(CBV)中和抗体效价明显高于献血员、风心病、冠心病及平均年龄基本配对的先心病组。效价≥1:320者亦明显高于其他4组,结果提示不明原因早搏与CBV感染可能有一定关系。     

胶体金免疫层析检测犬、猫抗狂犬病病毒IgG抗体的研究

目的建立检测犬、猫抗狂犬病病毒(RV)IgG抗体的胶体金免疫层析方法。方法采用柠檬酸三钠还原法制备胶体金用以标记SPA,同时将重组RVN蛋白、抗SPA抗体分别包被至硝酸纤维素膜的检测线与质控线上,制备一种检测犬、猫抗RVIgG抗体的胶体金检测卡,进行了特异性和灵敏度试验,并与ELISA同时检测临床样品、统计结果。结果 GICA试纸条检测灵敏度为0.5IU/mL,与犬瘟热病毒、犬细小病毒等阳性血清无交叉反应,并与ELISA相比,两者的符合率为94.6%。结论成功建立了检测犬、猫抗RVIgG抗体的通用型胶体金免疫层析方法 ,该方法灵敏度高,特异性强,检测速度快,操作简便,可广泛应用于基层。     

狂犬病疫苗不同免疫程序抗体测定

狂犬病疫苗不同免疫程序抗体测定河北平泉县卫生防疫站蔡荣河北承德市卫生防疫站刘长文河北承德医学院侯艳侠狂犬病是一种人畜共患病，近年来，狂犬病的发病呈上升趋势，疫区逐年扩大。目前降低发病率唯一的有效办法就是实施疫苗（ＲＶ）免疫。实际工作中发现，常规３０天...     

狂犬疫苗不同免疫程序后的抗体水平观察

狂犬病在世界上大多数国家均有存在,尽管人类对狂犬病的认识已有两千多年的历史,但至今这种人畜共患的病毒性传染病对人类仍是严重威胁。为了有效地预防狂犬病,探讨比较合理的免疫程序,我们对315例暴露者分别用常规五针法(下称五针法)和我们建立的连续十针法(下称十针法)两种不同方法免疫,对免疫后的抗体水平进行了比较,现报道如下。 材料与方法 —、疫苗及方法 疫苗采用长春生物制品研究所     

A Single Oral Immunization with Replication-Competent Adenovirus-Vectored Vaccine Induces a Neutralizing Antibody Response in Mice against Canine Distemper Virus

Canine Distemper Virus (CDV) is a fatal and highly contagious pathogen of multiple carnivores. While injectable vaccines are very effective in protecting domestic animals, their use in the wild is unrealistic. Alternative vaccines are therefore needed. Adenovirus (AdV) vectors are popular vaccine vectors due to their capacity to elicit potent humoral and cellular immune responses against the antigens they carry. In parallel, vaccines based on live human AdV-4 and -7 have been used in U.S. army for several decades as replicative oral vaccines against respiratory infection with the same viruses. Based on these observations, the use of oral administration of replication competent AdV-vectored vaccines has emerged as a promising tool especially for wildlife vaccination. Developing this type of vaccine is not easy, however, given the high host specificity of AdVs and their very low replication in non-target species. To overcome this problem, the feasibility of this approach was tested using mouse adenovirus 1 (MAV-1) in mice as vaccine vectors. First, different vaccine vectors expressing the entire or part H or F proteins of CDV were constructed. These different strains were then used as oral vaccines in BALB/c mice and the immune response to CDV was evaluated. Only the strain expressing the full length CDV H protein generated a detectable and neutralizing immune response to CDV. Secondly, using this strain, we were able to show that although this type of vaccine is sensitive to pre-existing immunity to the vector, a second oral administration of the same vaccine is able to boost the immune response against CDV. Overall, this study demonstrates the feasibility of using replicating AdVs as oral vaccine vectors to immunize against CDV in wildlife carnivores.     

Evaluation of Rapid Neutralizing Antibody Detection Test against Rabies Virus in Human Sera

Rapid and easy determination of protective neutralization antibody (NAb) against rabies in the field is very important for an early and effective response to rabies in both animal and human health sectors. The rapid neutralizing antibody detection test (RAPINA), first developed in 2009 and then improved in 2012, is a quick test allowing detection of 0.5 IU/ml antibodies in human and animal sera or plasma. This study aimed to assess the RAPINA test by comparison with rapid focus fluorescence inhibition test (RFFIT), using 214 sera of vaccinated and unvaccinated professional dog butchers, laboratory workers and rabies patients in Vietnam. The sensitivity, specificity, false negative rate, false positive rate and concordance of the RAPINA test as compared to RFFIT were 100%, 98.34%, 0%, 1.66% and 98.6%, respectively. The positive predictive value and negative predictive value were 91.7% and 100%, respectively when RAPINA test was used. With its remarkable sensitivity, specificity and easy implementation, RAPINA test can be used for rapid determination of NAb in the field.     

Hyperimmunized Chickens Produce Neutralizing Antibodies against SARS-CoV-2

The novel severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV-2, is responsible for the global COVID-19 pandemic. Effective interventions are urgently needed to mitigate the effects of COVID-19 and likely require multiple strategies. Egg-extracted antibody therapies are a low-cost and scalable strategy to protect at-risk individuals from SARS-CoV-2 infection. Commercial laying hens were hyperimmunized against the SARS-CoV-2 S1 protein using three different S1 recombinant proteins and three different doses. Sera and egg yolk were collected at three and six weeks after the second immunization for enzyme-linked immunosorbent assay and plaque-reduction neutralization assay to determine antigen-specific antibody titers and neutralizing antibody titers, respectively. In this study we demonstrate that hens hyperimmunized against the SARS-CoV-2 recombinant S1 and receptor binding domain (RBD) proteins produced neutralizing antibodies against SARS-CoV-2. We further demonstrate that antibody production was dependent on the dose and type of antigen administered. Our data suggests that antibodies purified from the egg yolk of hyperimmunized hens can be used as immunoprophylaxis in humans at risk of exposure to SARS-CoV-2.     

“攻击性”在犬类狂犬病监测和临床诊断中的作用与价值评估

目的 评估“攻击性”作为犬类狂犬病典型症状在监测和临床诊断中的作用与意义。方法 2011-2017年,从云南省收集到可疑狂犬病犬脑组织标本239份,使用DFA检验。将攻击性定义为咬人和动物总数≥2,并按可疑犬咬人和动物数,将可疑病犬分为“0”,“1”,“2”,“3”和“≥4”共5类。结果 239只可疑犬,总阳性率为64.02%;当咬人和动物数=0,1,2,3和≥4时,可疑犬阳性率分别为21.57%、61.76%、73.34%、77.50%和88.37%。当咬人和动物数≥2时,阳性率为78.57%。统计学分析显示:“1”类可疑犬阳性率与“2”和“3”类无统计学差异。结论 本研究结果支持WHO关于“攻击性”定义示例说明(咬两人或更多人或者动物和/或无生命物体),并为犬伤风险评估提供了参考数据。本研究建议未来犬类狂犬病监测项目的策划者和实施者在采用WHO目前关于“攻击性”的定义时,并关注咬人或动物数=1的可疑犬,如肇事犬死亡或逃逸,应深入调查其是否有吞食或咬或攻击异物(如石头、木块、移动车辆等)等异常行为。     

Neutralizing and Epitope-Specific Antibodies against Respiratory Syncytial Virus in Maternal and Cord Blood Paired Samples

Only a few qualitative studies of neutralizing antibody titers (NATs) against respiratory syncytial virus (RSV) have focused on epitope-specific antibody (ESA) levels. Here, NATs against RSV in sera were measured using the blood of 412 mothers and cord blood (CB) of 95 of the 412 mother–child pairs. ESA levels against sites zero (Ø) and IIa of the F protein of RSV were measured in 87 of the 95 mother–child pairs. The median gestational age was 39 weeks. The NATs and ESA levels in CB were slightly higher than those in maternal blood (MB). The NATs for RSV subtype A (RSV-A) in MB and CB showed a positive correlation (r = 0.75). The ESA levels against sites Ø and IIa in MB and CB showed positive correlations, r = 0.76 and r = 0.69, respectively. In MB, the NATs and ESA levels against RSV were positively correlated, more significantly against site Ø (RSV-A: r = 0.70, RSV-B: r = 0.48) than against site IIa (RSV-A: r = 0.19, RSV-B: r = 0.31). Sufficient amounts of ESAs against sites Ø and IIa of RSV were transferred from mothers to term infants. ESA levels against site Ø contribute to NATs.     

Neutralizing Monoclonal Anti-SARS-CoV-2 Antibodies Isolated from Immunized Rabbits Define Novel Vulnerable Spike-Protein Epitope

Monoclonal antibodies represent an important avenue for COVID-19 therapy and are routinely used for rapid and accessible diagnosis of SARS-CoV-2 infection. The recent emergence of SARS-CoV-2 genetic variants emphasized the need to enlarge the repertoire of antibodies that target diverse epitopes, the combination of which may improve immune-diagnostics, augment the efficiency of the immunotherapy and prevent selection of escape-mutants. Antigen-specific controlled immunization of experimental animals may elicit antibody repertoires that significantly differ from those generated in the context of the immune response mounted in the course of disease. Accordingly, rabbits were immunized by several recombinant antigens representing distinct domains of the viral spike protein and monoclonal antibodies were isolated from single cells obtained by cell sorting. Characterization of a panel of successfully isolated anti-receptor binding domain (RBD) and anti-N-terminal domain (NTD) antibodies demonstrated that they exhibit high specificity and affinity profiles. Anti-RBD antibodies revealing significant neutralizing potency against SARS-CoV-2 in vitro were found to target at least three distinct epitopes. Epitope mapping established that two of these antibodies recognized a novel epitope located on the surface of the RBD. We suggest that the antibodies isolated in this study are useful for designing SARS-CoV-2 diagnosis and therapy approaches.     

Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein’s receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.     

Characterization of a Broadly Neutralizing Monoclonal Antibody against SARS-CoV-2 Variants

The constant mutation of SARS-CoV-2 has led to the emergence of new variants, which call for urgent effective therapeutic interventions. The trimeric spike (S) protein of SARS-CoV-2 is highly immunogenic with the receptor-binding domain (RBD) that binds first to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and is therefore the target of many neutralizing antibodies. In this study, we characterized a broadly neutralizing monoclonal antibody (mAb) 9G8, which shows potent neutralization against the authentic SARS-CoV-2 wild-type (WT), Alpha (B.1.1.7), and Delta (1.617.2) viruses. Furthermore, mAb 9G8 also displayed a prominent neutralizing efficacy in the SARS-CoV-2 surrogate virus neutralization test (sVNT) against the Epsilon (B.1.429/7), Kappa (B.1.617.1), Gamma (P.1), Beta (B.1.351), and Delta Plus (1.617.2.1) RBD variants in addition to the variants mentioned above. Based on our in vitro escape mutant studies, we proved that the mutations V483F and Y489H within the RBD were involved in ACE2 binding and caused the neutralizing evasion of the virus from mAb 9G8. The development of such a cross-reactive neutralizing antibody against majority of the SARS-CoV-2 variants provides an important insight into pursuing future therapeutic agents for the prevention and treatment of COVID-19.     

Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort

The four dengue virus serotypes (DENV1–4) are mosquito-borne flaviviruses that infect ∼390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting.Dengue virus (DENV) is a mosquito-borne flavivirus that infects up to 390 million individuals each year (1). Although most infections are inapparent, ∼25% of infections cause acute febrile illness, which progresses to severe disease in half a million individuals annually (2). DENV consists of four evolutionarily distinct, antigenically related DENV serotypes, DENV1–4, and neutralizing antibodies (NAbs) against the four serotypes are considered a critical component of the protective immune response (3, 4). Primary (1°) DENV infection induces a NAb response that is described as increasingly type-specific over time, providing long-term protection against the 1° infecting serotype, but only transient protection against other DENV serotypes (5, 6). Cross-serotype protection against symptomatic infection is observed for up to 2 years after 1° infection, after which point individuals are at increased risk of symptomatic infection and severe dengue upon subsequent heterologous infection (7–10). Over time, cross-serotype–reactive antibodies are thought to decay to subneutralizing levels, binding, but not neutralizing, DENV and contributing to enhanced replication during heterologous infection by facilitating virus entry into target cells expressing Fc receptors (11). However, after subsequent infection with a different serotype, the NAb response becomes broadly neutralizing and is thought to reduce incidence of severe disease (12).There has been limited success in establishing the relationship between the level of preinfection NAb titers to DENV and risk of disease upon subsequent DENV infection in endemic settings. In recent vaccine trials, symptomatic disease was observed in individuals with relatively high NAb titers, raising concerns that the current immunologic assays do not measure the NAbs critical for protection (13). In studies of infants, who receive IgG antibodies by transplacental transfer from DENV-immune mothers, infants with higher NAb titers at birth generally, although not always, experienced symptomatic disease later than those with lower titers (14–16). Recent studies in children and adults have made important advances in demonstrating an association between the quantity of cross-reactive preinfection NAb titers and reduced risk of symptomatic secondary (2°) infection, defined as two or more infections, but have not been conclusive: the association did not hold for all DENV serotypes (15, 17); exposure could not be proven for DENV-negative individuals (18); or the magnitude of preinfection NAb titers was not directly studied (12, 19). Thus, there is an urgent need to definitively establish whether NAb titers correlate with protection in endemic settings. Here, we estimated the relationship between preinfection NAb titers and probability of symptomatic infection and characterized determinants of long-term protection in children with multiple DENV infections in a pediatric dengue cohort study in Nicaragua.