Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

Investigation of mumps vaccine failures in Minsk, Belarus, 2001-2003

The purpose of this study was to investigate mumps vaccine failures (VF) in a highly vaccinated population of Minsk, Belarus, and to investigate a possible role for virus strain-specific immunity. During our 3-year study period, 22 adults were admitted to the Infectious Diseases Hospital in Minsk with a diagnosis of mumps. A genotype H1 mumps virus (MuV) strain was identified in all patients. Of 15 patients from whom the paired sera were collected, 9 were confirmed to have been previously vaccinated. Serological examinations indicated primary VF in seven of these cases and secondary VF in two. Despite almost all vaccinated patients possessing MuV specific IgG, few possessed neutralizing antibody to the vaccine strain and titers were nominal. Importantly, none of the sera were able to neutralize a genotype H MuV strain. Our results demonstrate the importance of assaying for neutralizing antibody and support the assertion that antigenic differences between wild type and vaccine MuV strains may play a role in cases of breakthrough infection in vaccinees.     

Variability of hemagglutinin-neuraminidase and nucleocapsid protein of vaccine and wild-type mumps virus strains.

The mumps virus (MuV) molecular evolution is characterized by the co-circulation of numerous distinct strains. Standardized phylogenetic analyses based on the nucleotide sequences of the SH gene are important for mumps surveillance, but lack the information regarding antigenic properties. So far, the location of antigenic epitopes has been determined for two MuV proteins, the hemagglutinin-neuraminidase (HN) and the nucleocapsid (N) protein. We performed multiple sequence comparisons of putative HN and N protein sequences in order to describe their diversity and plasticity, and to determine the level of similarity between vaccine and wild-type strains. The results of full-length HN or N protein phylogeny showed that MuV strains form a number of differing clades which are in concordance with grouping obtained by standard MuV genotyping. When vaccine strains are compared to all wild-type strains, the highest mean percentage of amino acid differences in both HN and N protein analysis was found for Jeryl Lynn 5 and Jeryl Lynn 2 strains while the lowest value was obtained for Leningrad-3 and L-Zagreb strains. When only 3 antigenic regions of the HN protein, comprising 45 amino acids in total, were investigated, the diversity is considerably diminished: 51.5% of all putative HN proteins show identical sequences (including those of vaccine strains L-Zagreb, Leningrad-3, Hoshino and Urabe). Another 26.5% proteins (including Miyahara vaccine strain) differ in only one amino acid, while the others differ in two to five amino acids from the most common sequence. Jeryl Lynn 2 and Jeryl Lynn 5 strains differ in four amino acids each. N protein antigenic sites have been mapped within its hypervariable C-terminus. Our results indicate that there might be genotype-specific amino acids residing in this antigenic region. The results of our study present the background information for investigations of MuV heterogeneity and antigenic diversity.     

Serological and phylogenetic evidence of monotypic immune responses to different mumps virus strains

The recent resurgence of mumps epidemics in many countries with ongoing vaccination programs along with evidence of antigenic diversity among mumps virus strains have recently challenged the assumption that mumps virus is serologically monotypic. To address this controversy, we sought to identify two mumps virus strains that would best represent different serotypes, should multiple serotypes exist, and assess the ability of human sera to neutralize both strains. The virus strains, Enders and Lo1, were selected based upon a phylogenetic analysis of the major target of neutralizing antibody, the viral hemagglutinin-neuraminidase (HN) protein, along with data reported by others indicating that (1) these viruses are antigenically distinct and (2) genotypically similar strains have been implicated in cases of reinfection. Our results show that of sera capable of neutralizing one of the virus strains, 90% could neutralize the other, although significant differences in neutralization titers were noted. Though the latter confirms the existence of inter-strain antigenic variability, the fact that few sera were unable to neutralize both virus strains argues against the presence of multiple serotypes. Of those sera incapable of co-neutralization, all but one had low neutralization titers (1:8), suggesting that individuals possessing low levels of neutralizing antibody may be at risk for breakthrough infections, thereby providing an explanation for cases of infection in previously infected or vaccinated individuals.     

流行性腮腺炎病毒的分子流行病学研究

流行性腮腺炎(腮腺炎)是由腮腺炎病毒(MuV)引起的急性呼吸道传染病。截止2004年,MuV已发现了12个基因型,分别命名为A~L基因型。不同基因型MuV的分布具有地域性。研究表明,在同一地域的不同时期可能有不同基因型MuV在流行,在一个国家或地区也可能同时有不同基因型的MuV流行。MuV仅一个血清型,不同的MuV基因型之间有抗原交叉性,这种交叉性是至关重要的。可保护接种疫苗后的人群免受不同基因型MuV的感染。但有些体内和体外实验表明,基因型之间的抗原交叉性是有限的。流行病学数据还表明,某些毒株和基因型或基因型内某一组病毒具有神经毒性。近年来,调查了不同MuV的神经毒性,发现C、D、G、HI、、J基因型具有明确的神经毒性。但目前引起神经毒性的遗传学基础还不清楚。虽然,目前还无流行病学证据证明在不同的基因型或毒株之间出现抗原交叉性降低现象。但有数据表明,连续的进化和基因型的再分布在理论上可能导致神经毒力增强或交叉中和能力降低的毒株出现。因此,对MuV进行分子流行病学研究,了解基因型的分布,监测人群对基因型的特异性免疫是非常必要的。     

北京地区流行性腮腺炎野病毒与疫苗病毒基因特征比较

目的 比较北京地区流行性腮腺炎病毒流行株和疫苗株的基因特征,初步分析疫苗效果不佳的原因.方法 通过病例免疫史分析、病毒分离鉴定、SH基因序列分析,与其他基因型参考株进行同源性比较及血凝素-神经氨酸酶(HN)基因氨基酸关键位点变异分析.结果 病毒分离阳性病例共38例,其中IgM阴性7例.在2007和2008年,病毒分离率、RT-PCR阳性率、IgM抗体阳性率都有明显下降,同时有免疫史的病例增多.实验证明无免疫史的病例病毒分离和IgM抗体阳性率更高.38株病毒均属于F基因型,疫苗株属于A基因型.SH基因流行株之间核苷酸最大差异为5.6%,与疫苗株的差异为16.0%～18.1%.部分北京株SH蛋白中保守的疏水性氨基酸发生变化,如第8位:6株L→F.各流行株之间FIN蛋白氨基酸序列最大差异为2.3%,与疫苗株差异为4.2%～5.3%.在HN上决定交叉中和能力的氨基酸位点,北京株与疫苗株存在差异,如在354位和356位,所有北京株与疫苗株都不同.北京株在HN上的N-糖基化位点也和疫苗株存在差异,如在464～466位置上为NCS,疫苗株为NCR.另有18个未知功能的氨基酸位点,所有北京株与疫苗株不同.结论 近年北京地区流行的腮腺炎病毒优势株为F基因型,未发现基因型间变异,已存在较大型内差异.北京株和疫苗株在SH和HN蛋白上都存在较大差异.     

Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China

Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F.     

Genetic characterization of historical epidemic mumps viruses in northern Spain, 1987–1990

The mumps virus (MuV) is genetically diverse and is divided into 12 genotypes. The World Health Organization has recommended expanding virological surveillance for MuV, and therefore molecular characterization of circulating strains (i.e. genotypes) is increasingly performed. Nevertheless, little is known about the genotypes circulating before the massive vaccination of children and adolescents. The present study analyzed the strains causing the 1988–1989 mumps epidemic in the Basque Country, northern Spain, which occurred in the early vaccination period, before the endemic circulation of mumps virus was blocked. The epidemic reached an annual incidence rate of more than 400 cases/100,000 inhabitants, and caused a large number of cases of mumps meningitis. MuV RNA was amplified from the cerebrospinal fluid of 15 infected patients during the epidemic and from three more patients affected shortly before or after this epidemic (1987, early 1988 and 1990). Genotyping of the complete small hydrophobic gene (316 nucleotides), amplified in the 18 strains, as well as of the entire hemagglutinin-neuraminidase gene (1749 nucleotides), amplified in four strains, assigned all strains to genotype K, a genotype infrequently detected at present. Although the putative HN protein sequence differed by 4.8–5.5% in relation to Jeryl Lynn 5 strain (the main strain used in the vaccination program in this region), the vaccine was effective, and dramatically reduced the incidence of mumps over the following years. The presence of genotype K strains in Spain in the 1980s, together with their contemporary detection in Scandinavia, suggests that this genotype could have caused the Spanish epidemic and was also circulating widely in Europe at that time.     

Mumps-specific cross-neutralization by MMR vaccine-induced antibodies predicts protection against mumps virus infection

BackgroundSimilar to other recent mumps genotype G outbreaks worldwide, most mumps patients during the recent mumps genotype G outbreaks in the Netherlands had received 2 doses of measles, mumps and rubella (MMR) vaccine during childhood. Here, we investigate the capacity of vaccine-induced antibodies to neutralize wild type mumps virus strains, including mumps virus genotype G.MethodsIn this study, we tested 105 pre-outbreak serum samples from students who had received 2 MMR vaccine doses and who had no mumps virus infection (n = 76), symptomatic mumps virus infection (n = 10) or asymptomatic mumps virus infection (n = 19) during the mumps outbreaks. In all samples, mumps-specific IgG concentrations were measured by multiplex immunoassay and neutralization titers were measured against the Jeryl Lynn vaccine strain and against wild type genotype G and genotype D mumps virus strains.ResultsThe correlation between mumps-specific IgG concentrations and neutralization titers against Jeryl Lynn was poor, which suggests that IgG concentrations do not adequately represent immunological protection against mumps virus infection by antibody neutralization. Pre-outbreak neutralization titers in infected persons were significantly lower against genotype G than against the vaccine strain. Furthermore, antibody neutralization of wild type mumps virus genotype G and genotype D was significantly reduced in pre-outbreak samples from infected persons as compared with non-infected persons. No statistically significant difference was found for the vaccine strain. The sensitivity/specificity ratio was largest for neutralization of the genotype G strain as compared with the genotype D strain and the vaccine strain.ConclusionsThe reduced neutralization of wild type mumps virus strains in MMR vaccinated persons prior to infection indicates that pre-outbreak mumps virus neutralization is partly strain-specific and that neutralization differs between infected and non-infected persons. Therefore, we recommend the use of wild type mumps virus neutralization assays as preferred tool for surveillance of protection against mumps virus infection.     

The molecular epidemiology of mumps virus.

The molecular epidemiology of MuV is characterized by the co-existence of 10 (or more) distinct genotypes named A-J based on the nucleotide sequence of the SH gene. MuV show distinct geographic clustering. More than one genotype may circulate simultaneously in a geographic region. Limited data suggest redistribution of genotypes to occur over time. The selective forces remain speculative. Currently used vaccine strains belong to different genotypes. Some MuV genotypes (C, D, H, J) and vaccine strains (Urabe Am9) have been associated with enhanced neurovirulence. Also, reduced cross-neutralization capacity has been observed between genotype A and genotypes C and D. At present vaccine failure cannot be attributed to this phenomenon. Strain redistribution may lead to the emergence of new MuV strains with enhanced neurovirulence or reduced cross-neutralization capacity with current vaccine strains. Close monitoring of the genotype distribution of MuV and genotype-specific population immunity is needed in the vaccine era.     

麻疹-流行性腮腺炎-风疹联合减毒活疫苗与流行性腮腺炎减毒活疫苗免疫学效果比较

目的比较麻疹-流行性腮腺炎（流腮）-风疹联合减毒活疫苗（Measles,Mumps and Rubella Combined Attenuated Live Vaccine;MMR）与流腮减毒活疫苗（Mumps Attenuated Live Vaccine,MuV）的免疫学效果。方法在宝鸡市选取18-24月龄未患过流腮、无MuV或含流腮成分疫苗免疫史、无接种禁忌证的健康儿童作为观察对象,将其按照所属乡分为两组,采集免疫前血清后分别接种MMR和MuV,1个月后采集免疫后血清检测流腮免疫球蛋白（Immunoglobulin,Ig）G。结果接种MMR的流腮IgG阳性率由免疫前的9.4%上升至98.8%,阳转率为98.8%,几何平均浓度（Geometric Mean Concentration,GMC）由免疫前的54.8单位（Unit,U）/毫升（ml）上升到1380.8 U/ml,增长24.2倍。接种MuV的流腮IgG阳性率由免疫前的8.3%上升至94.0%,阳转率为89.3%,GMC由免疫前的70.5 U/ml上升到611.1 U/ml,增长7.67倍。结论接种MMR和MuV均有良好的对流腮的免疫学效果。     

不同免疫策略下流行性腮腺炎发病特症的初步比较分析

目的分析采取不同免疫策略的地区流行性腮腺炎（流腮）疫情趋势,探讨不同免疫策略下流腮的流行病学特征。方法利用描述流行病学分析方法,对常规免疫实施两剂含流腮成分疫苗（Mumps-containing Vaccine,Mu CV）免疫策略的北京、天津、上海三个市和全国其他地区流腮疫情资料以及突发公共卫生事件信息进行分析。结果2004-2011年,全国流腮报告发病率呈逐年上升趋势。2008年以来,三个市流腮报告发病率呈下降趋势。全国流腮疫情呈规律的季节分布,每年存在冬季和夏季两个发病高峰,北京和上海市仅夏季高发。流腮报告发病率最高为5-9岁儿童,2008-2011年三个市5-9岁儿童流腮发病率较2004-2007年平均水平大幅下降,全国5-9岁儿童流腮发病率呈逐年上升趋势。2009年以来,三个市报告流腮突发公共卫生事件起数大幅下降并维持在低水平。结论实行两剂Mu CV常规免疫,有助于降低流腮高发人群发病率,有效地控制爆发疫情的发生。     

Genomic characterization of mumps viruses from a large-scale mumps outbreak in Arkansas, 2016

In 2016, a year-long large-scale mumps outbreak occurred in Arkansas among a highly-vaccinated population. A total of 2954 mumps cases were identified during this outbreak. The majority of cases (1676 (57%)) were school-aged children (5–17 years), 1536 (92%) of these children had completed the mumps vaccination schedule. To weigh the possibility that the mumps virus evaded vaccine-induced immunity in the affected Arkansas population, we established a pipeline for genomic characterization of the outbreak strains. Our pipeline produces whole-genome sequences along with phylogenetic analysis of the outbreak mumps virus strains. We collected buccal swab samples of patients who tested positive for the mumps virus during the 2016 Arkansas outbreak, and used the portable Oxford Nanopore Technology to sequence the extracted strains. Our pipeline identified the genotype of the Arkansas mumps strains as genotype G and presented a genome-based phylogenetic tree with superior resolution to a standard small hydrophobic (SH) gene-based tree. We phylogenetically compared the Arkansas whole-genome sequences to all publicly available mumps strains. While these analyses show that the Arkansas mumps strains are evolutionarily distinct from the vaccine strains, we observed no correlation between vaccination history and phylogenetic grouping. Furthermore, we predicted potential B-cell epitopes encoded by the Arkansas mumps strains using a random forest prediction model trained on antibody-antigen protein structures. Over half of the predicted epitopes of the Jeryl-Lynn vaccine strains in the Hemagglutinin-Neuraminidase (HN) surface glycoprotein (a major target of neutralizing antibodies) region are missing in the Arkansas mumps strains. In-silico analyses of potential epitopes may indicate that the Arkansas mumps strains display antigens with reduced immunogenicity, which may contribute to reduced vaccine effectiveness. However, our in-silico findings should be assessed by robust experiments such as cross neutralization assays. Metadata analysis showed that vaccination history had no effect on the evolution of the Arkansas mumps strains during this outbreak. We conclude that the driving force behind the spread of the mumps virus in the 2016 Arkansas outbreak remains undetermined.     

云南省2007--2009年流行性腮腺炎病毒SH和HN基因的遗传特征分析

目的 分析2007-2009年云南省腮腺炎病毒(MuV)分离株的SH和HN遗传特征.方法 采用反转录-聚合酶链反应从Vero细胞分离的病毒株基因组中扩增出SH基因和HN基因,测序后用Mega4.1软件分析其遗传特征.结果 云南省分离14株MuV的SH基因其核苷酸和氨基酸同源性为98.3%～100.0%和96.5%～100.0%,与其他省份比较其同源性为92.6%～99.4%和87.7%～100.0%,其中Wsh1和Wsh2与其他F基因型差异较大;与疫苗株同源性为84.5%～85.1%和77.2%;与其他基因型同源性为83.4%～90.9%和70.1%～86.0%.6株MuV分离株的HN基因与核苷酸和氨基酸同源性分别为99.3%～99.5%和99.1%～99.7%;与中国分离株SP株的核苷酸和氨基酸同源性均为99.8%;与其他基因型同源性为94.7%～96.8%和95.5%～99.1%;与疫苗株的同源性为92.4%～93.2%和95.5%～96.4%.结论 2007-2009年云南省流行的MuV均为F基因型;其HN基因比SH基因保守.

Abstract：

Objective To analyze genetic characterization of the small hydrophobic and hemagglutinin-neuraminidase genes of mumps virus(MuV)isolated in Yunnan province,China from 2007 to 2009.Methods Fourteen MuV strains were isolated in Yunnan,China from 2007 to 2009.Using RT-PCR,the SH gene fragments contained 316 nucleotides in all strains and HN gene of six strains were sequenced.The sequences were aligned with other mumps virus sequences downloaded from GenBank using Mega 4.1 software.Results Fourteen isolated strains were closely related to other reference strains of F genotypes.In SH gene,the homology of nucleotide and amino acid among the fourteen isolated strains were 98.3%-100.0%and 96.5%-100.0%,respectively,and 92.6%%-99.4%and 87.7%-100.0% of homology when compared with that of strains isolated from other provinces in China,respectively.Wsh1 and Wsh2 strains had less homology when compared to other strains of F genotypes.The fourteen strains had homology of 84.5%-85.1%and 77.2%compared to vaccine strains on nucleotide and amino acid,respectively,and had homology of 83.4%-90.9% and 70.1%-86.0% compared to that of other genotypes.In HN gene,the homology of nucleotide and amino acid among the six isolated strains were 99.3%-99.5% and 99.1%-99.7%,respectively,and also 99.8% and 99.8% of homology respectively when compared to the SP strain in China.All the six strains had homology of 92.4%-93.2% and 95.5%-96.4% when compared to the vaecine strains on nucleotide and amino acid,respectively,and had homology of 94.7%-96.8% and 95.5%-99.1%compared to other genotypes.Conclusion Fourteen strains isolated in Yunnan from 2007 to 2009belonged to F genotype of MuV while the HN gene seemed more conservative than SH gene.     

Generation of a recombinant Oka varicella vaccine expressing mumps virus hemagglutinin-neuraminidase protein as a polyvalent live vaccine

We constructed a recombinant varicella-zoster virus (VZV) Oka vaccine strain (vOka) that contained the mumps virus (MuV) hemagglutinin-neuraminidase (HN) gene, inserted into the site of the ORF 13 gene by using the bacterial artificial chromosome (BAC) system in Escherichia coli. Insertion of the HN gene into the VZV genome was confirmed by PCR and Southern blot. The infectious virus reconstituted from the vOka-HN genome (rvOka-HN) had a growth curve similar to the original recombinant vOka without the HN gene. The mumps virus HN protein expressed in rvOka-HN infected cells was expressed diffusely in the cytoplasm, and modification of the protein was similar to that seen in MuV-infected cells. Electron microscopic examination of infected cells revealed that HN was expressed on the plasma membrane of the cells but not in the viral envelope, suggesting that the tropism of rvOka-HN would be unchanged from that of the original vOka strain. Immunization of guinea pigs with rvOka-HN-induced VZV- and HN-specific antibodies. Interestingly, the induced antibodies had a strong neutralizing activity against virus-cell infections of both MuV and VZV. Therefore, the novel varicella vaccine expressing MuV HN protein is suitable as a polyvalent live attenuated vaccine against VZV and MuV infections.     

2005-2019年广州市流行性腮腺炎突破病例流行病学分析

目的 了解广州市流行性腮腺炎突破病例的流行病学特征,分析含流腮成分疫苗接种对流行性腮腺炎的影响.方法 对2005-2019年广州市流行性腮腺炎突破病例进行流行病学特征分析.结果 2005-2019年广州市流行性腮腺炎突破病例为13 180例,占同期总病例数的19.5％且该占比呈现逐年波折向上趋势,从2005年的3.26...     

Complete genome sequence of mumps viruses isolated from patients with parotitis,pancreatitis and encephalitis in India

Limited information is available regarding epidemiology of mumps in India. Mumps vaccine is not included in the Universal Immunization Program of India. The complete genome sequences of Indian mumps virus (MuV) isolates are not available, hence this study was performed. Five isolates from bilateral parotitis and pancreatitis patients from Maharashtra, a MuV isolate from unilateral parotitis patient from Tamil Nadu, and a MuV isolate from encephalitis patient from Uttar Pradesh were genotyped by the standard protocol of the World Health Organization and subsequently complete genomes were sequenced. Indian MuV genomes were compared with published MuV genomes, including reference genotypes and eight vaccine strains for the genetic differences. The SH gene analysis revealed that five MuV isolates belonged to genotype C and two belonged to genotype G strains. The percent nucleotide divergence (PND) was 1.1% amongst five MuV genotype C strains and 2.2% amongst two MuV genotype G strains. A comparison with widely used mumps Jeryl Lynn vaccine strain revealed that Indian mumps isolates had 54, 54, 53, 49, 49, 38, and 49 amino acid substitutions in Chennai-2012, Kushinagar-2013, Pune-2008, Osmanabad-2012a, Osmanabad-2012b, Pune-1986 and Pune-2012, respectively. This study reports the complete genome sequences of Indian MuV strains obtained in years 1986, 2008, 2012 and 2013 that may be useful for further studies in India and globally.     

Hypervariable antigenic region 1 of classical swine fever virus E2 protein impacts antibody neutralization

Envelope glycoprotein E2 of classical swine fever virus (CSFV) is the major antigen that induces neutralizing antibodies and confers protection against CSFV infection. There are three hypervariable antigenic regions (HAR1, HAR2 and HAR3) of E2 that are different between the group 1 vaccine C-strain and group 2 clinical isolates. This study was aimed to characterize the antigenic epitope region recognized by monoclonal antibody 4F4 (mAb-4F4) that is present in the group 2 field isolate HZ1-08, but not in the C-strain, and examine its impact on neutralization titers when antisera from different recombinant viruses were cross-examined. Indirect ELISA with C-strain E2-based chimeric proteins carrying the three HAR regions showed that the mAb-4F4 bound to HAR1 from HZ1-08 E2, but not to HAR2 or HAR3, indicating that the specific epitope is located in the HAR1 region. Of the 6 major residues differences between C-strain and field isolates, Glu713 in the HAR1 region of strain HZ1-08 is critical for mAb-4F4 binding either at the recombinant protein level or using intact recombinant viruses carrying single mutations. C-strain-based recombinant viruses carrying the most antigenic part of E2 or HAR1 from strain HZ1-08 remained non-pathogenic to pigs and induced good antibody responses. By cross-neutralization assay, we observed that the anti-C-strain serum lost most of its neutralization capacity to RecC-HZ-E2 and QZ-14 (subgroup 2.1d field isolate in 2014), and vice versa. More importantly, the RecC-HAR1 virus remained competent in neutralizing ReC-HZ-E2 and QZ-14 strains without compromising the neutralization capability to the recombinant C-strain. Thus, we propose that chimeric C-strain carrying the HAR1 region of field isolates is a good vaccine candidate for classical swine fever.     

浙江省麻疹野毒株抗原性变异分析

目的 了解浙江省麻疹野毒株的抗原性变异状况。方法 采用麻疹病毒标准株Edmonston、疫苗株沪19l与近几年浙江省分离的麻疹野毒株(浙江／5／98和浙江/4/2000)分别制备免疫血清，与各毒株进行交叉中和试验。结果 麻疹野毒株浙江／5／98与疫苗株沪19l和Edm株的抗原比分别为3．0和2．6，浙江/4/2000与上述3毒株的抗原比分别为7．3和5．65，其抗原性存在着明显的差异。结论 浙江省麻疹野毒株已出现明显的抗原性变异。     

不同人群血清对麻疹疫苗株与流行株的中和能力比较

目的探讨不同人群血清对麻疹流行株与疫苗株中和能力的差异。方法采集麻疹患者急性期与恢复期血清、麻疹疫苗免疫前后儿童血清以及流动人口血清，分别对疫苗株沪191与2005年麻疹流行株进行中和抗体（NT）滴度测定。同时，利用疫苗株、浙江省当地流行株制备动物免疫血清，与相应毒株进行交叉中和试验，测定各毒株之间抗原比。结果疫苗免疫后儿童血清对疫苗株的中和抗体几何平均滴度（GMT）为50.82，高于流行株MVi／ZJ／05／7（GMT值为27．35）1．86倍；患者恢复期血清对流行株的中和能力（GMT值为386．95）显著高于疫苗株（GMT值为151．83）；流动人口血清对流行株中和抗体GMT值均小于疫苗株，差异为2．22～4．17倍；MVi／ZJ／99／1、MVi／ZJ／04／1和MVi／ZJ／05／7与疫苗株间抗原比分别为4．28、5．24和5．66。此外，部分患者急性期血清对疫苗株存在低滴度的中和抗体，GMT值1：4左右。结论不同人群血清对麻疹疫苗株与流行株的中和能力的差异有统计学意义，低滴度的疫苗抗体不能有效保护个体免受麻疹流行毒株的侵袭，应加强麻疹病毒变异与疫苗效果的相关研究。