Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region, China, 2018.

Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends (+2.63% per year; P < 0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.

G2 rotavirus within an emergent VP7 evolutionary lineage circulating in children with acute diarrhea in Guangxi Province of China, 2014.

Routine surveillance revealed that the prevalence of P[4] rotaviruses circulating in children with acute diarrhea in Guangxi Province, China, increased in 2014. However, VP7 genotyping for these P[4] rotaviruses was unsuccessful. Exhaustive database searching and sequence analysis indicated that the G genotype of these P[4] rotaviruses was G2, and the VP7 genes clustered with recently emerging G2 strains in several countries within an emergent evolutionary lineage that was distinct from the previously designated lineages I-IV as well as lineage V including porcine rotaviruses. Further studies are essential to monitor the potential global spread of this emerging G2 rotavirus.

Immunogenicity, safety, and immune persistence of a novel inactivated human enterovirus 71 vaccine: a phase II, Randomized, double-blind, placebo-controlled Trial.

BACKGROUND: Vaccination is considered a top priority for the control of human enterovirus 71 (EV71) infection outbreaks. METHODS: On the basis of phase I trial results, we conducted a double-blind, randomized, controlled trial to evaluate the optimal dose, immunogenicity, safety and immune persistence of the vaccine. A total of 480 healthy infants were randomly assigned to receive 2 injections of 100 U of vaccine, 200 U of vaccine, 400 U of vaccine, or placebo. Solicited adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each vaccination were collected for safety evaluation. Blood samples were collected for neutralizing antibody assay. RESULTS: EV71 vaccine was well tolerated, and no dose-related safety concerns were observed. Two doses of the vaccine yielded seropositivity frequencies of 92.3%, 95.9%, and 99.0% (with titers ≥1:8) in the 100 U, 200 U, and 400 U groups, respectively. Geometric mean titers measured by neutralizing antibody assay increased to 60.2 (95% confidence interval [CI], 41.9-86.4), 72.8 (95% CI, 50.8-104.3), and 252.1 (95% CI, 180.8-351.6) for the 100 U, 200 U, and 400 U groups, respectively. The dose-response relationship, with the 400 U dose showing higher immunogenicity than the 100 U and 200 U doses, remained until 13 months after the second vaccination, despite waning antibody levels. CONCLUSIONS: The 400 U dose was recommended as the optimal dose for the phase III trial because of its good safety profile and higher immunogenicity.

Amino acid polymorphism in the reverse transcriptase region of hepatitis B virus and the relationship with nucleos(t)ide analogues treatment for preventing mother-to-infant transmission.

A high maternal serum hepatitis B virus (HBV) DNA level is associated with vaccine failure. The administration of nucleos(t)ide analogues (NAs) in pregnancy for decreasing serum HBV is regarded as an effective and safe method to reduce HBV perinatal transmission. However, the effect of NAs treatment is closely related to amino acid polymorphisms in the HBV reverse transcriptase (RT) region. The full-length RT coding region of 334 HBV isolates from untreated Chinese women of childbearing age with persistent HBV infection were sequenced and amino acid polymorphic analysis was performed to evaluate its impact on NAs treatment for decreasing HBV perinatal transmission. Of the 334 isolates, 36 (10.8%) harbored NAs resistance (NAr) mutations which were mainly putative drug mutations related to lamivudine. The primary drug mutation rtA181T/V was detected in three HBeAg-negative women with an HBV DNA level of <4 log IU/ml. These NAr mutations were rarely detected in women with an HBV DNA level of ≥7 log IU/ml (P = 0.014) or in women younger than 35 years (P = 0.001). The NAr mutation rate among young women (<35 years) who had a high HBV DNA level (≥7 log IU/ml) was significantly lower than in women who had lower HBV DNA levels (<7 log IU/ml) or who were older (≥35 years; P = 0.017). These results suggest that younger women with a high HBV DNA level harbor fewer NAr mutations and that this population may respond to NAs treatment for the prevention of mother-to-infant transmission.

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: The current influenza pandemic calls for a safe and effective vaccine. We assessed the safety and immunogenicity of eight formulations of 2009 pandemic influenza A H1N1 vaccine produced by ten Chinese manufacturers. METHODS: In this multicentre, double-blind, randomised trial, 12 691 people aged 3 years or older were recruited in ten centres in China. In each centre, participants were stratified by age and randomly assigned by a random number table to receive one of several vaccine formulations or placebo. The study assessed eight formulations: split-virion formulation containing 7.5 microg, 15 microg, or 30 microg haemagglutinin per dose, with or without aluminium hydroxide adjuvant, and whole-virion formulation containing 5 microg or 10 microg haemagglutinin per dose, with adjuvant. All formulations were produced from the reassortant strain X-179A (A/California/07/2009-A/PR/8/34). We analysed the safety (adverse events), immunogenicity (geometric mean titre [GMT] of haemagglutination inhibition antibody), and seroprotection (GMT >or=1:40) of the formulations. Analysis was by per protocol. Two sites registered their trial with ClinicalTrials.gov, numbers NCT00956111 and NCT00975572. The other eight studies were registered with the State Food and Drug Administration of China. FINDINGS: 12 691 participants received the first dose on day 0, and 12 348 participants received the second dose on day 21. The seroprotection rate 21 days after the first dose of vaccine ranged from 69.5% (95% CI 65.9-72.8) for the 7.5 microg adjuvant split-virion formulation to 92.8% (91.9-93.6) for the 30 microg non-adjuvant split-virion formulation. The seroprotection rate was 86.5% (796 of 920; 84.1-88.7) in recipients of one dose of the 7.5 microg non-adjuvant split-virion vaccine compared with 9.8% (140 of 1432; 8.3-11.4) in recipients of placebo (p<0.0001). One dose of the 7.5 microg non-adjuvant split-virion vaccine induced seroprotection in 178 of 232 children (aged 3 years to <12 years; 76.7%, 70.7-82.0), 211 of 218 adolescents (12 years to <18 years; 96.8%, 93.5-98.7), 289 of 323 adults (18-60 years; 89.5%, 85.6-92.6), and 118 of 147 adults older than 60 years (80.3%, 72.9-86.4), meeting the European Union's licensure criteria for seroprotection in all age-groups. In children, a second dose of the 7.5 microg formulation increased the seroprotection rate to 97.7% (215 of 220, 94.8-99.3). Adverse reactions were mostly mild or moderate, and self-limited. Severe adverse effects occurred in 69 (0.6%, 0.5-0.8) recipients of vaccine compared with one recipient (0.1%, 0-0.2) of placebo. The most common severe adverse reaction was fever, which occurred in 25 (0.22%; 0.14-0.33) recipients of vaccine after the first dose and four (0.04%; 0.01-0.09) recipients of vaccine after the second dose compared with no recipients of placebo after either dose. INTERPRETATION: One dose of non-adjuvant split-virion vaccine containing 7.5 microg haemagglutinin could be promoted as the formulation of choice against 2009 pandemic influenza A H1N1 for people aged 12 years or older. In children (aged <12 years), two 7.5 mug doses might be needed. FUNDING: Sinovac Biotech, Hualan Biological Bacterin, China National Biotec Group, Beijing Tiantan Biological Products, Changchun Institute of Biological Products, Changchun Changsheng Life Sciences, Jiangsu Yanshen Biological Technology Stock, Zhejiang Tianyuan Bio-Pharmaceutical, Lanzhou Institute of Biological Products, Shanghai Institute of Biological Products, and Dalian Aleph Biomedical.

Burden and etiology of moderate and severe diarrhea in children less than 5 years of age living in north and south of China: Prospective, population-based surveillance.

BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.

Immunogenicity of an Escherichia coli-produced bivalent human papillomavirus vaccine under different vaccination intervals.

A new Escherichia coli-produced human papillomavirus (HPV)-16/18 vaccine has been shown to be safe and highly efficacious and was recently licensed in China. As a post hoc analysis of the phase III trial, this study aimed to assess the impact of vaccination time deviations on the specific antibody response and guide the better usage of this vaccine in the real world. A total of 3689 healthy women aged 18-45 years old were randomly assigned to receive the bivalent HPV-16/18 vaccine according to a 0-, 1- and 6-month schedule with a wide vaccination interval. The first vaccination interval between the 1st and 2nd doses (the 1st interval) was divided into three groups: 28-40 d, 41-50 d and 51-60 d. The second vaccination interval between the 2nd and 3rd doses (the 2nd interval) was divided into three groups: 103-139 d, 140-160 d and 161-198 d. The reverse cumulative curves for the IgG of the three groups with different 1st vaccination intervals or with different 2nd vaccination intervals at month 7 almost overlapped for both HPV-16 and HPV-18. Compared with the standard vaccination schedule (a 1st interval of 28-40 d and a 2nd interval of 140-160 d) subgroup, all the subgroups had GMC ratios greater than 0.83, with the lower limit of 95% CIs higher than 0.64. In conclusion, a slight deviation in the vaccination time of the 2nd and 3rd doses has only a minor, insignificant impact on the immune response induced by the Escherichia coli-produced HPV-16/18 vaccine.

Lot-to-lot consistency study of an Escherichia coli-produced bivalent human papillomavirus vaccine in adult women: a randomized trial.

An Escherichia. coli-produced HPV-16/18 bivalent vaccine has been proved to be well-tolerated and highly efficacious against diseases associated with vaccine HPV types. As a part of the multi-center, randomized, double-blind phase III clinical trial, this lot-to-lot consistency study aimed to assess the safety and immunogenicity consistency of this novel HPV vaccine, which is also one of the objectives of the phase III trial. A total of 3689 healthy women aged 18-45 years were enrolled and randomly assigned 1:1:1 to three lots of the HPV vaccine groups. The primary outcomes were the IgG antibody level at 1 month after the last dose (month 7). In the immunogenicity per-protocol set (PPS), almost all of the participants seroconverted at month 7 and remained seropositive at month 42. For each paired comparison of the three lot groups, the two-sides of 90% CIs of GMC ratios for both IgG and neutralizing antibodies for HPV-16 and HPV-18 at month 7 were within the equivalence interval [0.5, 2]. Lot consistency was also demonstrated at month 42. The majority of recorded solicited reactions were mild or moderate. The incidences of solicited reactions of Lot 2 and Lot 3 were slightly higher than Lot 1. However, the incidences of solicited reactions of ≥ grade 3 and solicited reactions by symptoms were all similar among the three lot groups. None of the SAEs was considered related to vaccination by the investigator. In conclusion, this study demonstrates lot-to-lot consistency of the 3 consecutive lots of the E. coli-produced HPV-16/18 bivalent vaccine.

Burden of viral gastroenteritis in children living in rural China: Population-based surveillance.

BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

[Effectiveness of inactivated poliomyelitis vaccine for primary vaccination].

OBJECTIVE: To study the immunological effectiveness of inactivated poliomyelitis vaccine (IPV) for children's primary vaccination in China and to compare with the oral poliomyelitis vaccine (OPV) used in routine vaccination. METHODS: The 2-month-old children were randomly immunized with IPV and OPV, with 208 subjects in each group. The pre- and post-vaccination blood samples were collected. Micro-neutralization method was used to measure the antibody response against 3 types of polioviruses. chi2 test was used to evaluate the statistical difference of protection rates between two groups, while the antibody titers were transformed by logarithm and analyzed by Z-test. P < 0.05 was always used to define the significance of analysis. RESULTS: After 3 doses of immunization, the protection rates in IPV group reached to 100.0% (186/186), 97.3% (181/186), 98.9% (184/186) for poliovirus type 1, 2, 3, respectively, and in OPV group were 97.4% (188/193), 100.0% (193/193), 95.3% (184/193), respectively. The geometry mean titers (GMTs) were 151.2, 86.7, 211.3 for IPV group; and 1089.5, 538.2, 203.7 for OPV group. IPV showed comparable protection rates with OPV for type 1 and 2 (chi2(I) = 2.991, P = 0.084; chi2(II) = 3.512, P = 0.061), while type 3 was higher than OPV (chi2(III) = 4.143, P = 0.042). The GMT of type 1 and 2 in IPV group were lower than OPV group (Z(I) = 12.537, P = 0.000; Z(II) = 13.415, P = 0.000), while the GMT of type 3 were comparable in two groups (Z(III) = 0.067, P = 0.947). CONCLUSION: IPV showed roughly comparable immunological effectiveness in young children. The protection rates for type 1 and 2 were similar to OPV, while type 3 was higher than in OPV group; In terms of GMT,type 1 and 2 in IPV group were lower than OPV, but type 3 were comparable to OPV group.

[Establishment and preliminary application of a gene chip for detection of hepatitis B virus "a" determinant hotpoint mutation].

OBJECTIVE: To develop a gene chip for rapid detection of the "a" determinant hotpoint mutation of hepatitis B virus (HBV). METHODS: Primers were designed in the HBV conservative region, and probes for detecting 126A, 126S, 144A, 145R, 145E, 144A+145R, and 144A+145E mutants were developed for that gene chip. PCR amplification and gene chip technology were optimized. The performance of the gene chip was evaluated by detecting the reference plasmids. Forty five samples of serum obtained from patients with chronic hepatitis B were used to compare the sensitivity of the gene chip and the direct sequencing of PCR products. RESULTS: The oligonucleotide microarray was specific for mutant and native plasmids. The sensitivity of the gene chip was 5 x 10(3)copies/micro l with a high reproducibility. The gene chip could detect minor variants when they were more than 10% among the HBV strains. The positive rates of 126A, 126S-1, 126S-2 detected in the 45 specimens by the gene chip (46.67%, 35.56% and 24.44%, respectively) were higher than those detected by direct sequencing of PCR products (9.00%, 4.44% and 2.22%; P=0.000, P=0.000 and P=0.002, respectively). The sequencing of cloned PCR products demonstrated that the gene chip was specific for the "a" determinant hotpoint mutation detection. CONCLUSION: HBV "a" determinant hotpoint mutations can be detected by oligonucleotide microarray with high sensitivity and specificity, providing a method for large scale screening of the mutants.

Hepatitis B vaccine alone may be enough for preventing hepatitis B virus transmission in neonates of HBsAg (+)/HBeAg (-) mothers.

BACKGROUND AND AIM: To prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers. METHODS: Combined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (-) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (-) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6months with or without HBIG at birth. RESULTS: At 7months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p=1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p=0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7months of age (1555.3mIU/mL vs. 654.9mIU/mL, p<0.0001). At 12months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p=0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7mIU/mL vs. 297.0mIU/mL, p=0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12months of age. CONCLUSIONS: Vaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers.

Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants.

We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2-3-4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18-24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1-3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile.

Immunogenicity of Two Different Sequential Schedules of Inactivated Polio Vaccine Followed by Oral Polio Vaccine Versus Oral Polio Vaccine Alone in Healthy Infants in China.

BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule. METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored. RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar. CONCLUSIONS: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants.

This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6-16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9-79.9) and 64.2% (95% CI: 55.4-72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5-77.1) and 50.0% (95% CI: 40.9-59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines.

Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China.

INTRODUCTION: The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7). METHODS AND ANALYSIS: 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12-15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed. ETHICS AND DISSEMINATION: Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance. TRIAL REGISTRATION NUMBER: NCT02736240.

[Core promoter mutations of HBV isolated from patients with chronic hepatitis B in Guangxi].

OBJECTIVE: To explore the relationship between HBV core promoter mutations and liver damage or HBeAg status. METHODS: Nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA core promoter in 59 sera from patients with chronic hepatitis B in Guangxi, then the HBV DNA positive products were sequenced by direct sequencing. RESULTS: The HBV DNA positive rate of was 59.3%(35/59). All the patients were infected by mutants. The commonest mutation was the double mutation (A --> T at nt1762 and G --> A at nt1764), counting for 57.1% (20/35). The next was C --> G at nt1799, counting for 54.4% (19/35), but this was no function. A --> G at nt1752 (resulting in isoleucine to valine) was seen in 37.1% (13/35) of the HBV DNA positive patients, and T --> C at nt1753 was seen in 20% (7/35). The significant difference in the frequency of T1762A1764 mutant was found between HBeAg positive patients (31.3%) and negative patients (79.0%). CONCLUSIONS: HBV core promoter mutations are common among patients with chronic hepatitis B in Guangxi. T1762A1764 mutant is associated with HBeAg status and chronic hepatitis.