[Immunogenicity and safety of a booster dose of inactivated polio vaccine].

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.

[Study of immunogenicity after primary vaccination by different sequential program of inactivated poliovirus vaccine and oral poliovirus vaccine].

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.

[Study on the Fast Testing Strategy for identifying the wild poliovirus I].

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.

[Genetic characteristics of enterovirus 71 isolated in Beijing, 2006-2008].

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.

[Human enterovirus 71 was isolated from specimens of hand foot mouth disease in Beijing in 2007].

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.

[Analysis of polio antibody levels in healthy population in Beijing in 2007].

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.

[Study on the etiology of hand-foot-mouth disease outbreaks in Beijing in 2007].

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.