RESUMEN
OBJECTIVE: To investigate the genetic variability and the epidemiological features of respiratory syncytial virus (RSV) in Beijing during five consecutive seasons from 2015 to 2019. METHODS: We collected 36,927 samples (ages ranged from 1 day to 101 years old) from cases with acute respiratory tract infections (ARTI) using the Respiratory Pathogens Surveillance System (RPSS) in Beijing, 2015-2019. G gene sequencing and phylogenetic analysis were performed to identify RSV genotypes, clusters, and amino acid (aa) changes. RESULTS: In total, 764 (2.1%, 764/36927) cases were RSV positive, 52.1% cases were children under 5 years old, and 25.8% were elderly ≥ 60 years old. We obtained 369 sequences of the G gene. ON1 and BA9 were the dominant genotypes in Beijing. Sub-lineage 4 of ON1, which contains four aa substitutions (T113I, N178G, H258Q, and H266L), emerged in 2017 and became the predominant variant in 2018-2019. Sub-lineage 4 of BA9, which contains two aa changes (A131T, T137I), emerged in 2017 and became the predominant variant in 2019. We also observed 10 rarely reported nucleotide deletions in the 3' end of the G gene from five sequences of the ON1 genotype. CONCLUSION: With the exception of children < 5 years old, RSV infection mainly occurred in the elderly ≥ 60 years old. Newly emerged sub-lineages have replaced existing sub-lineage over time and become predominant in Beijing. Continued surveillance of the genetic diversity of RSV is necessary.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Anciano , Beijing/epidemiología , Niño , Preescolar , Variación Genética , Genotipo , Humanos , Lactante , Persona de Mediana Edad , Filogenia , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genéticaRESUMEN
To investigate the seroepidemiological features of enterovirus D68 (EV-D68) in the healthy population from 2012 to 2017 in Beijing, China. A retrospective cross-sectional investigation was conducted using serum specimens collected from healthy individuals in Beijing from 2012 to 2017. These samples were tested for neutralization antibodies (NtAbs) against EV-D68. The sera from six EV-D68 infected patients in the acute or convalescent phase were used to determine the protection level of NtAbs against EV-D68. The geometric means of the titers (GMT) of EV-D68 NtAbs in 2012 and 2017 were 92.82 and 242.91, respectively; the seroprevalences of EV-D68 were 89.43% and 98.43%, respectively. The GMT reached its peak in the 11 to 15 age group in 2012, while in 16 to 20 age group in 2017. We also observed that EV-D68 NtAbs titers of six sera from the acute phase were all less than equal to 1:64 and that of three sera from the convalescent phase were all more than 1:64. Anti-EV-D68 NtAbs in the population remained low from 2012 to 2016 but increased significantly in 2017. Although most of the EV-D68 infections remain undetected in Beijing, the risk of a large outbreak of EV-D68 exists and should be taken seriously.
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Enterovirus Humano D/inmunología , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Beijing/epidemiología , Niño , Preescolar , Estudios Transversales , Brotes de Enfermedades , Enterovirus Humano D/clasificación , Enterovirus Humano D/genética , Infecciones por Enterovirus/sangre , Infecciones por Enterovirus/virología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Filogenia , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
In 2000, China was declared polio-free. However, in 2018, wild poliovirus (WPV) was still endemic in two of its neighboring countries, making WPV importation and outbreak alarming possibilities. This study documents the seroprevalence of poliovirus antibodies before and after the polio vaccine switch in 2012 and 2017 in Beijing. Cross-sectional population-based serologic surveys were conducted in 2012 and 2017 in Beijing. The study subjects were selected from 10 different age groups (<1, 1-4, 5-9, 10-14, 15-19, 20-24, 25-29, 30-34, 35-39, and ≥40 y) using a multi-stage-stratified sampling method. Neutralizing antibody titers against poliovirus serotypes 1 (P1), 2 (P2), and 3 (P3) were assayed by World Health Organization standards. The seropositive rates (SR) and geometric mean titer (GMT) of the neutralizing antibodies were 91.71% and 1:130.26, respectively, for P1, 94.09% and 1:113.39, respectively, for P2, and 88.78% and 1:79.65, respectively, for P3 before the switch in 2012, and 87.78% and 1:108.93, respectively, for P1, and 81.67% and 1:70.56, respectively, for P3 after the switch in 2017, with a statistically significant difference for P1 and P3 between 2012 and 2017. The neutralizing antibodies for all poliovirus serotypes differed among different age and vaccination groups in both 2012 and 2017. After switching polio vaccines twice in 2014 and 2016, the P1 and P3 polio antibody levels were lower in 2017 than in 2012. The P2 antibody levels were determined from the first dose of IPV. The seroprevalence of poliovirus antibodies after adjustment of the immunization schedule of the polio vaccine on January 1, 2020, must be further monitored.
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Poliomielitis , Vacunas contra Poliovirus , Poliovirus , Anticuerpos Antivirales , Beijing , China/epidemiología , Estudios Transversales , Humanos , Lactante , Poliomielitis/epidemiología , Poliomielitis/prevención & control , Vacuna Antipolio de Virus Inactivados , Vacuna Antipolio Oral , Estudios Seroepidemiológicos , VacunaciónRESUMEN
BACKGROUND: OPV is the only poliovirus vaccine used in the China EPI system, although IPV is available in the private market. We compared immunigencity and persistence among different schedules of IPV and OPV. METHODS: 536 Chinese infants were enrolled into 4 groups receiving different schedules administered at 2, 3, and 4 months of age: IPV-OPV-OPV, IPV-IPV-OPV, IPV-IPV-IPV, and OPV-OPV-OPV. The I-I-I group received an 18-month IPV booster dose. Blood samples were collected before the first dose, after the third dose, and at 18 months for all groups, and also after the booster dose for the I-I-I group. Polio neutralizing antibody titers were assessed, and seroprotection rates were calculated after primary immunization and at 18 months of age. RESULTS: Before the first dose, GMTs of the 4 groups ranged from 2.96 to 6.89, and seroprotection rates ranged from 17.6% to 54.3%. After 3 doses, the GMT of the I-O-O and I-I-O groups ranged from 901.09 to 1,110.12, and the GMT of the I-I-I group range was 212.02 to 537.52, significantly lower than for the 2 sequential schedules (P<0.001). Seroprotection rates were 98.1% to 100%, with no significant differences among groups. At 18 months of age, the GMTs declined to a range of 527.00 to 683.44 in the I-O-O and I-I-O groups, and declined to 150.04 to 239.89 in the I-I-I group, significantly lower than for the other 3 groups (P<0.001). CONCLUSIONS: The sequential schedules achieved high GMTs and seroprotection. The IPV-only schedule achieved high seroprotection but with lower GMTs. Sequential schedules are suitable for China. With the 2 sequential schedules, GMTs remained high at 18 months of age and were not inferior to the OPV-only schedule. Thus, with a sequential schedule, the booster dose could be given at 4 years of age, the same age as the current OPV booster dose.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Esquemas de Inmunización , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio Oral/administración & dosificación , Vacuna Antipolio Oral/inmunología , China , Femenino , Humanos , Lactante , Masculino , Factores de TiempoRESUMEN
OBJECTIVE: To analyze the polio immunity level of persistent population in Beijing, 2012. METHODS: A total of 1 676 subjects residing more than 6 months in Beijing were selected by stratified random cluster sampling design in 2012. Demographic characteristics, history of oral poliovirus vaccine (OPV) immunization were investigated by questionnaire. All 5 ml blood sample were collected for testing of polio neutralizing antibody using the method of microcell neutralization. The positive rate and the geometric mean titer (GMT) of polio neutralizing antibody type I, II and III were analyzed in different groups. RESULTS: The positive rate of type I, II and III were 98.2% (1 645/1 676), 98.1% (1 644/1 676), 97.6% (1 635/1 676); The GMT were 1:130.2, 1: 113.4 and 1: 79.7. Three types of positive rates in<15 years group (99.7% (664/666), 99.8% (665/666), 99.5% (663/666)) were higher than those of ≥ 15 years group (97.1% (981/1 010), 96.9% (979/1 010), 96.2% (972/1 010)), the differences were significant (all the values of P < 0.01); The GMT in<15 years group (1:325.9, 1:250.5, 1:190.7) were higher than that of ≥ 15 years group (1: 71.1, 1: 67.2, 1: 44.8), the difference was significant (all the values of P < 0.01). The positive rate (99.0%-100%) and GMT (1: 128.8-1: 300.7) in vaccination information confirmed population were higher. The highest positive rate (all were 100%) and GMT(1: 409.7-1: 636.7) were observed in children who vaccinated three times. CONCLUSION: The polio antibody of healthy population was at a high level in Beijing in 2012; Especially the age groups of < 15 years which were covered by vaccines.Immunization barrier had been formed firmly to interrupt the transmission of wild poliovirus and vaccine-derived poliovirus.
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Vacunación/estadística & datos numéricos , Inmunidad Adaptativa , Adolescente , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Niño , Humanos , Poliomielitis , Poliovirus , Vacuna Antipolio OralRESUMEN
OBJECTIVE: To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine (IPV) among children aged 18 months who had been administered with primary doses of IPV. METHODS: Form 2011 to 2012, a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2, 3, 4 months of age and boosted with the same vaccine at 18 months of age. Anti-poliovirus neutralizing antibody titers in serum were measured before and after booster vaccination, geometric mean titers (GMT) and seroprotection rate were calculated. Adverse events occurring within 30 days after booster vaccination were observed, including pain, redness/swelling and induration at the injection site, fever, vomit, abnormal crying, drowsiness, loss of appetite, irritability, and all other physical discomfort and related medications were also recorded. A descriptive analysis was performed for the safety assessment. RESULTS: Immunogenicity was assessed in 84 subjects. The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1, 2, 3 before booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 148.5 (116.49-189.29) , 1: 237.68 (178.39-316.67) and 1: 231.87 (181.27-296.58) , respectively. The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 1612.14 (1470.57-1767.34) , 1: 1854.92 (1715.83-2005.29) and 1: 1625.50 (1452.12-1819.58) , respectively. The pre-booster titer of neutralizing antibody against poliovirus type 1, 2, 3 mainly ranged 1: 128-1: 512, which accounted for 65% (55/84) , 55% (46/84) , 74% (62/84) in each type. After the booster immunization, titers of neutralizing antibody against type 1, 2, 3 were increased as subjects with titer ≥ 1: 1024 accounted for 94% (78/84) , 95% (80/84) , 92% (77/84) , respectively.Safety was evaluated in 96 subjects, of which 16 subjects reported adverse events with the rate of 17%. The observed local events were mainly tenderness 3% (3/96) , redness/swelling and induration were not reported. The systemic adverse events included loss of appetite (8%, 8/96) , irritability (8%, 8/96) , fever (7%, 7/96) , abnormal crying (6%, 6/96) , drowsiness (6%, 6/96) and vomit (1%, 1/96) . All reported adverse events were mild or moderate. All of the local events occurred in the day of vaccination and lasted for 1-2 days, while systemic events almost developed within 2 days after vaccination and last less than 3 days. CONCLUSION: IPV booster dose has good immunogenicity and safety profile, which provides effective protection against poliovirus.
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Poliomielitis/prevención & control , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/uso terapéutico , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , China , Femenino , Humanos , Inmunización Secundaria/efectos adversos , Lactante , Masculino , Vacuna Antipolio de Virus Inactivados/efectos adversosRESUMEN
OBJECTIVE: To evaluate immunogenicity after primary vaccination by different sequential program of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). METHODS: Children of 2 months old (60-89 days) selected in Beijing were assigned to 4 groups, 1 dose IPV plus 2 doses OPV (I-O-O, 122 children), 2 doses IPV plus 1 dose OPV(I-I-O, 103 children), 3 doses IPV (I-I-I, 114 children), and 3 doses OPV (O-O-O, 106 children), and were vaccinated at the age of 2, 3, 4 months. Polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested and protective rates were calculated before the 1st dose, after the last dose, and after the 1st and 2nd dose of IPV. RESULTS: After the primary immunization, geometric mean titers (GMT) of polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were 788.32, 738.42 and 631.17 in O-O-O group, 212.02, 262.30 and 537.52 in I-I-I group, 940.35, 929.72 and 940.35 in I-O-O group and 901.09, 1102.68 and 1110.12 in I-I-O group (F values were 47.71, 53.84, and 9.81 respectively, all P values<0.01). The protective rate of three types among each group was 98.1% (104/106)-100.0% and the difference was not statistically significant (P>0.05). After the 1(st) dose of IPV, the GMT were 18.88, 37.77, 24.64 and the protective rate was 82.6% (122/138)-96.4% (133/138); after the 2nd dose of IPV, GMT were 177.03, 168.25, 321.86 and the protective rate was 99.1% (108/109)-100.0% (109/109) in antibody types 1, 2 and 3, respectively. CONCLUSION: GMT of polio neutralizing antibody titers against poliovirus is higher after vaccination by sequential program of IPV and OPV than that by IPV or OPV 3-doses program. High level of protective rate after 2 doses of IPV in I-I-O group may lead to better protection from vaccine associated paralytic poliomyelitis (VAPP). Sequential program of IPV and OPV can be used to maintain high level of herd immunity and to prevent VAPP, and the I-I-O sequential program should be the first choice.
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Esquemas de Inmunización , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio Oral/inmunología , Vacunas Atenuadas/inmunología , Humanos , Lactante , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio Oral/administración & dosificaciónRESUMEN
OBJECTIVE: To explore the Fast Testing Sstrategy (FTS) for wild poliovirus I (WP1). METHODS: Epidemiological investigations were carried out on 671 students from WP1 epidemic areas in China. A set of real time RT-PCR assays, including panenterovirus testings (PE) assay, poliovirus serotypings (PS) assay and the assay distinguishing wild strain from vaccine strain of poliovirus I (DWV) were introduced into the screening program for WPV1 to replace the conventional RT-PCR, recommended by the China National Polio Laboratory (GNPL). Additionally, sensitivities of all the assays were assessed by poliovirus type I to III (Sabin stain) and the isolated WPV1. RESULTS: (1) 33 non-poliovirus enterovirus (NPEV) cases were detected, with 16 polio vaccine-related cases including 5 polio I, 1 polio II, 3 polio III, 1 polio I + II, 4 polio I + III and 2 polio I + II + III. Three WPV1 cases were also detected in this study and confirmed by CNPL. (2) For polio virus vaccine strain, sensitivities of the set of real time RT-PCR assays ranged from 1 to 100 times than that of the in-house RT-PCR assay. The sensitivities of PE and PS assays for the detection of polio II were 100 times than that of the RT-PCR assay and the sensitivity of DWV assay used for the detection of polio I were 10 times than that of the RT-PCR assay. For WPV1, the sensitivity of three real time RT-PCR was 10 times hight than that of the RT-PCR assay. CONCLUSION: The novel FTS for WPV1 suggested by this study would include PE, PS and DWV. It not only could greatly shorten the testing time but also more sensitive than the RT-PCR and suited for emergency detection for WPV1.
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Poliomielitis/diagnóstico , Poliovirus/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , China/epidemiología , Enterovirus , Epidemias , Humanos , Poliomielitis/epidemiología , Poliovirus/clasificación , Vacunas contra Poliovirus , Sensibilidad y EspecificidadRESUMEN
Enterovirus 71 (EV71) is the most important causative agent of hand, foot and mouth disease (HFMD) in children. In most cases, it is a self-limiting illness. However some EV71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. To identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 5'-NTR and 3'-NTR in 25 SC-EV71 strains (strains from severe cases) and 31 MC-EV71 strains (strains from mild cases) were analyzed. Results showed four amino acids on two positions (Gly(P710)/Gln(P710)/Arg(P710) and Glu(P729)) on the DE and EF loop of VP1, one (Lys(P930)) on the surface of protease 2A and four nucleotides on three positions (G(P272), U(P488) and A(P700)/U(P700)) in the 5'-NTR region are associated with EV71 virulent phenotype. Predicted secondary structure of RNA using the consensus sequence of 5'-NTR by RNAStructure showed the mutation of nucleotide at position 488 in strain BJ08-Z004-3 (position 491 in prototype strain BrCr) can result in the discrepancy of an additional pair of nucleotides and thus change the stability of the second structure of IRES. Fragment base content analysis showed that in the region 696 to 714 bp at the 5'-NTR, where the A(P700)/U(P700) was located, the nucleotide constitution ratios differed significantly between SC-EV71 and MC-EV71 strains. In conclusion, comparative genomic analysis showed that virulence of EV71 strains are mainly determined by the amino acids on two positions of VP1, one position of protease 2A and the nucleotides on three positions in 5'-NTR.
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Enterovirus/genética , Virulencia/fisiología , Línea Celular , Enterovirus/clasificación , Enterovirus/patogenicidad , Humanos , Modelos Moleculares , FilogeniaRESUMEN
OBJECTIVE: To sequence and analyze the VP1 region of isolated enterovirus from different sources in Beijing, 2006-2008. METHODS: 9 EV71 were selected from the isolates identified through the specimen of human hand foot mouth disease (HFMD), acute flaccid paralysis (AFP) and healthy children in Beijing, 2006-2008. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to amplify and sequence the whole VP1 gene of enterovirus. Phylogenetic tree was constructed, with the means of nucleotide homology and distance between/within groups analyzed. RESULTS: The 9 selected strains were clustered with C4 subgenotype reference strains in Phylogenetic tree and showed high nucleotide acid identity (92.1%-93.9% ) in nucleotide homology analysis, and had higher homology than C1, C2, C3 subgenotype reference strains (88.8%-89.5%, 89.4%-90.0% and 88.4%-89.3%, respectively). High homologous (95.9%-100.0%) was noticed between the isolated stains from three different sources, but low homologous (93.3% -93.9%, 92.1%-92.9%, respectively) showed between the isolated stains and C4 reference strains isolated in 1998. There appeared larger variations between groups in C4 subgenotype when analyzing the distance between groups means, especially between the reference strains and isolated strains (D = 0.052-0.071). CONCLUSION: The EV71 isolated in Beijing, from 2006 to 2008 also appeared to be C4 subgenotype and there was no significant difference found in the whole sequence of VP1 gene of the strains isolated from different regions, sources, or under different diseases occurred in the same period. There were more nucleotide variations and more chances for the presence of new subgenotype, suggesting that it is necessary to strengthen the surveillance program on EV71 isolates.
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Proteínas de la Cápside/genética , Infecciones por Enterovirus/virología , Enterovirus/genética , Enfermedad de Boca, Mano y Pie/virología , Secuencia de Bases , Niño , China , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Genes Virales , Genotipo , Humanos , Filogenia , ARN Viral/genética , Análisis de Secuencia de ARNRESUMEN
OBJECTIVE: Analyzing and identifying the type of enterovirus of human Hand Foot Mouth Disease (HFMD) outbreak in Daxing district in Beijing at the end of May in 2007. METHODS: The liquid of Herpes, throat swab and stool specimen were collected. Using reverse transcription-polymerase chain reaction (RT-PCR) method to amplify the enterovirus specific nucleotide acid fragment from specimens and virus positive cultures, the sensitivity of two methods was compared. Then identifying and typing of the enterovirus of HFMD through analyzing the results of nucleotide sequencing of the virus positive cultures. RESULTS: In 10 specimens from 5 HFMD children patients, enterovirus specific nucleotide acid fragment was detected in 8 patients, the RT-PCR positive ratio (80%) was higher than enterovirus isolation positive ratio (30%). In 5 enteroviruses isolated from 5 patients and 9 close contacts, 4 isolated from 2 patients and 1 close contact were Enterovirus 71.1 isolated from close contact was Coxsackievirus A16. CONCLUSION: Enterovirus 71 was the pathogen of HFMD outbreak in Daxing district at the end of May in 2007.
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Enterovirus Humano A/aislamiento & purificación , Heces/virología , Enfermedad de Boca, Mano y Pie/virología , Faringe/virología , Línea Celular , China , Enterovirus Humano A/genética , Enfermedad de Boca, Mano y Pie/transmisión , HumanosRESUMEN
OBJECTIVE: To identify the etiology of 8 human hand-foot-mouth disease (HFMD) outbreaks in Beijing, during May to July 2007. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) method was used to directly type the specimens including fluid from the herpes and throat swabs from the HFMD patients. Using RD cell lines, the collected stool specimens were cultured followed by typing. Partial VP1 region of selected EV positive specimens and cultures were sequenced and both nucleic acid sequence and predicted amino acid sequence were analyzed. RESULTS: The two HFMD outbreaks in Daxing region in Beijing in 2007 were caused by enterovirus 71 type (EV71), and the others were caused by Coxsackie virus A16 (Cox A16). Two EV71 strains caused epidemics in Daxing region in 2007 belonged to C4 subgenotype but on different branches in VP1 gene phylogenetic tree. The differences on nucleic acid sequence and amino acid sequence were 3.7% and 0.8% between the two EV71 stains, respectively. The Cox A16 strain in Shunyi region and the other strains were on different branches in phylogenetic tree, and the difference on nucleic acid and amino acid sequence were 3.7% and 0% respectively between the two Cox A16 stains. CONCLUSION: The HFMD outbreaks occurred in Beijing in 2007 were caused mainly by EV71 and Cox A16, and there were two individual epidemic virus strains. Cox A16 seemed to spread more widely than EV71 in Beijing, 2007.
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Brotes de Enfermedades , Enterovirus Humano A/genética , Enfermedad de Boca, Mano y Pie/etiología , Secuencia de Aminoácidos , China/epidemiología , Enterovirus Humano A/clasificación , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Humanos , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de SecuenciaRESUMEN
OBJECTIVE: To investigate the poliomyelitis antibody level in healthy people in Beijing. METHODS: 10 age groups (0, 1 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and > or = 40) were sampled by the Multi-stage stratified sampling method in 7 districts in Beijing, and 1552 sera from healthy population were collected. The poliomyelitis antibody was determined with microcell neutralization method. RESULTS: The neutralized antibody-positive rate for polio I, II, III were 97.04%, 97.29% and 91.04% respectively, the geometric mean titers (GMT) were 1:70.05, 1:54.60, and 1:31.83 respectively. A trend of decreasing was observed in the GMTs with increasing age and years after immunization. There were no significant differences in antibody levels between different gender, residents or regions. The results of multiple-factors analysis showed that the GMTs were significantly associated with age and the years after immunization. CONCLUSION: A stable immunization barrier has been established in healthy population in Beijing.