Immunogenicity and safety of a new hexavalent rotavirus vaccine in Chinese infants: A randomized, double-blind, placebo-controlled phase 2 clinical trial.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.

Efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache with concomitant nonalcoholic fatty liver disease in climacteric women.

OBJECTIVE: This study aimed to assess the efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache (CTTH) with concomitant nonalcoholic fatty liver disease (NAFLD) in climacteric women. METHODS: In this study, we enrolled 150 climacteric women with CTTH and concomitant NAFLD. The participants were divided into three groups based on the random number table: medication group, acupuncture group, and acupuncture-medication group. Treatment continued for 2 months. The efficacy of CTTH was assessed based on the visual analog scale/score (VAS). The influence on NAFLD was assessed based on body mass index (BMI), controlled attenuation parameter (CAP), and the ratio of hepatic-splenic computed tomography (CT) value. The Participant Health Questionnaire-9 (PHQ-9) score was compared among the three groups. RESULTS: A total of 123 participants completed the trial, including 37 participants in the medication group, 41 participants in the acupuncture group, and 45 participants in the acupuncture-medication group. Results are summarized hereinafter. (1) The total clinical efficiency rates of the medication group, acupuncture group, and acupuncture-medication group were 89.19% (33 of 37), 90.24% (37 of 41), and 95.65% (44 of 46), respectively. (2) Except for the BMI of the medication group ( P = 0.063), a significant difference in VAS, BMI, CAP, the ratio of hepatic-splenic CT value, and PHQ-9 score was found in the three groups ( P < 0.01). (3) There was a significant difference in VAS, BMI, CAP, and PHQ-9 among the three groups ( P < 0.01), with those in the acupuncture-medication group being superior. No difference in the ratio of hepatic-splenic CT value was found ( P = 0.440). (4) The efficacy differed significantly among the three groups ( χ2 = 8.130, P = 0.017), and it was significantly superior in the acupuncture-medication group ( P = 0.008, P = 0.013). CONCLUSIONS: Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in treating CTTH in climacteric women compared with either acupuncture or medication. Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in subsiding the negative moods in participants with CTTH and concomitant NAFLD.

Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Safety of the 15-valent pneumococcal conjugate vaccine: A phase I clinical trial.

To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhu & Co. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (≥18 years) and 20 children (1-5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.

The efficacy of acupuncture combined with Bailemian capsule in the treatment of cervical spondylosis accompanied by headache, anxiety, and depression.

OBJECTIVE: The present study aimed to investigate the efficacy of using acupuncture combined with Bailemian capsule to treat cervical spondylosis by observing the improvement in the degree of headache, anxiety, and depression suffered by patients. METHODS: A total of 100 patients with cervical spondylosis of the cervical type were equally divided into a combination group and a control group using the random number table method. The patients in the combination group were treated with acupuncture combined with the oral administration of Bailemian capsule, while those in the control group were only treated with acupuncture. Patient self-assessment was conducted, comprising the visual analogue scale, the self-assessment scale for anxiety, and the self-assessment scale for depression. Before treatment and on the14th and 28th days of treatment, the therapeutic effects of the two treatment modalities on the cervical spondylosis and accompanying headache, anxiety, and depression were analyzed using the Hamilton anxiety scale, the Hamilton depression scale, the Pittsburgh sleep quality inventory, and the Neck Disability Index (%). RESULTS: There were statistically significant differences between the two groups in all seven indicators at the different treatment time points (p < 0.01). The seven indicators were significantly reduced in both groups on the 14th and 28th days of treatment compared with before the treatment. Moreover, except for the Neck Disability Index results at 14 days, which did not differ between the groups (p = 0.37), all the other indicators were significantly lower in the combination group than in the control group on the 14th and 28th days of treatment (p < 0.01), and at the end of the treatment, the therapeutic effect was significantly better in the combination group than in the control group (p = 0.006). CONCLUSION: Both acupuncture combined with Bailemian Capsule and acupuncture alone were effective in the treatment of cervical spondylosis, but the combination therapy was better than the acupuncture alone in improving the accompanying negative symptoms of headache, anxiety, and depression.

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.

Safety and immunogenicity of a novel oral hexavalent rotavirus vaccine：a phase I clinical trial.

Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity.Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6-12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA).Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups.Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.

Genetic susceptibility to rotavirus infection in Chinese children: a population-based case-control study.

Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case-control study nested in a population-based diarrhea surveillance targeting children <5 y of age was performed in rural Hebei province, north China. Saliva and serum samples were collected from all participants to determine HBGA phenotyping, FUT2 mutations, and RV IgG antibody titers. A logistic model was employed to assess the association between host HBGA secretor status and risk of RV infection. Among 235 RV cases and 680 non-diarrhea controls studied, 82.4% of participants were IgG positive by an average age of 77 months. Out of the 235 RV cases, 216 (91.9%) were secretors, whereas the secretor rate was 76.3% in the non-diarrhea controls, resulted in an adjusted OR of 3.0 (95%CI: 1.9-4.7, P < .0001) between the two groups. Our population-based case-control study indicated a strong association between host HBGA secretor status and risk of RV infection in Chinese children. The high prevalence of Lewis-positive secretor status strongly suggests that Chinese children may be genetically susceptible to current co-circulating RV strains, and thus, a universal childhood immunization program against RV disease should be successful in China.

Immune response to different types of hepatitis B vaccine booster doses 2-32 years after the primary immunization schedule and its influencing factors.

OBJECTIVE: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2-32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters. METHODS: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs. RESULTS: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.8 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups. CONCLUSIONS: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI ≥ 25 and prebooster anti-HBs concentration <2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection.

Long-term protection at 20-31 years after primary vaccination with plasma-derived hepatitis B vaccine in a Chinese rural community.

Background: To assess the long-term protection conferred by plasma-derived hepatitis B vaccine at 20-31y after primary immunization during infancy in Chinese rural community.Method: Participants born between 1986 and 1996, who received a full course of primary vaccination with plasma-derived hepatitis B vaccine and had no experience with booster vaccination were enrolled. An epidemiological investigation was performed, and blood samples were collected to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). The positive rate of HBsAg, anti-HBs, and anti-HBc were calculated to evaluate the long-term protection of the plasma-derived hepatitis B vaccine.Results: A total of 949 participants were enrolled in the final analysis. Six subjects were detected to be HBsAg-positive, resulting in a HBsAg carrier rate of 0.63% (6/949). A total of 468 (52.41%) participants maintained a level of anti-HBs antibody ≥10 mIU/mL, with a GMC of 112.20 mIU/mL (95%CI: 97.72 ~ 128.82 mIU/mL). A significant downtrend was observed in the anti-HBs positive rate (P < .001). The average anti-HBc positive rate was 5.90% (56/949), increased with prolongation of immunization (P < .001).Conclusions: The plasma-derived hepatitis B vaccine maintained satisfactory protection at 20-31 y after primary immunization. These results indicate that a booster dose is not necessary. Further studies on the immune memory induced by the plasma-derived hepatitis B vaccine are needed.

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.

Immune persistence 17 to 20 years after primary vaccination with recombination hepatitis B vaccine (CHO) and the effect of booster dose vaccination.

BACKGROUND: To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life. METHODS: Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects. RESULTS: A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC). CONCLUSION: Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17-20 years ago was demonstrated, there is currently no urgent need for booster immunization.

Elemental analysis and imaging of sunscreen fingermarks by X-ray fluorescence.

Chemical composition in fingermarks could provide useful information for forensic studies and applications. Here, we evaluate the feasibility of analysis and imaging of fingermarks via elements by synchrotron radiation X-ray fluorescence (SRXRF) and commercial X-ray fluorescence (XRF). As a proof of concept, we chose four brands of sunscreens to make fingermarks on different substrates, including plastic film, glass, paper, and silicon wafer. We obtained an evident image of fingermarks via zinc and titanium by XRF methods. In addition, the ratios of element concentrations in sunscreen fingermarks were obtained, which were in accordance with the results obtained by acid digestion and ICP-OES analysis. In comparison, commercial XRF offers the most advantages in terms of non-destructive detection, easy accessibility, fast element images, and broad applicability. The possibility to acquire fingermark images simultaneously with element information opens up new avenues for forensic science. Graphical abstract.

Biological effects of autophagy in mice with sepsis-induced acute kidney injury.

This study investigated whether autophagy is activated after sepsis-induced acute kidney injury (AKI) and explored its biological role. Seventy-two normal C57 mice were randomly divided into sham operation group, cecal ligation and puncture (CLP) group and CLP+3-MA (autophagy inhibitor) group; 24 mice in each group. Mice in CLP and CLP+3-MA group were treated with cecal ligation to establish sepsis, while mice in sham operation group were treated with the same surgical operations, but not cecal ligation. Blood samples were collected from 12 mice of each group and the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. The pathological changes were observed. The remaining 12 mice in each group were kept and the survival rate was recorded. Changes in the expressions of autophagy-related proteins were detected by reverse transcription-semi-quantitative PCR and western blotting. The results revealed that the levels of Cr and BUN in CLP and CLP+3-MA group were significantly higher than those in sham operation group (P<0.05), and the levels of Cr and BUN in CLP+3-MA group were higher than those in CLP group (P<0.05). The pathological score of renal injury in CLP+3-MA group was significantly higher than that of CLP group (P<0.01). The expression levels of Beclin1 and LC3-II/I were significantly increased in CLP group compared to sham operation group (P<0.01), while the expression of p62 was decreased (P<0.01). After 3-MA treatment the expression levels of Beclin1 and LC3-II/I were decreased, compared with CLP group, but accumulation of p62 occurred, and the degree of renal injury was increased. In conclusion, AKI induced by sepsis in mice can induce apoptosis and activate autophagy. The activation of autophagy aggravates the renal injury in mice, which in turn inhibits AKI after sepsis.

Expression changes of autophagy-related proteins in AKI patients treated with CRRT and their effects on prognosis of adult and elderly patients.

BACKGROUND: Sepsis is one of the common death factors in intensive care unit, which refers to the systemic inflammatory response syndrome caused by infection. It has many complications such as acute renal injury, shock, multiple organ dysfunction, and failure. The mortality of acute renal injury is the highest among the complications, which is a serious threat to the safety of patients and affects the quality of life. This study aimed to observe the changes in autophagy-related protein expressions in patients with acute kidney injury (AKI) after continuous renal replacement therapy (CRRT) and their impacts on prognosis. METHODS: 207 AKI patients visiting the Emergency Department of The First People's Hospital of Xuzhou from January 2014 to February 2018 were recruited and treated with CRRT. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to detect the expression of autophagy-related genes, including light chain 3 type II (LC3-II), autophagy-related 5 (Atg-5) and Beclin-1, in the monocytes of the patient's peripheral blood before and after treatment. The levels of inflammatory mediators interleukin (IL)-1ß and IL-6 were determined via enzyme-linked immunosorbent assay before and after treatment. The patient's serum creatinine (Scr) level before and after treatment was measured using a full-automatic biochemistry analyser. Moreover, the treatment effect was graded after CRRT, and the relationship between the prognosis of patients and the autophagy-related proteins was observed. RESULTS: The Scr levels in the patients were significantly decreased after treatment with CRRT. Before treatment, the IL-1ß and IL-6 blood levels were high in the patients, while the amounts were significantly reduced after CRTT. The expressions of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients after treatment were significantly decreased compared with those before treatment. Compared with those in survived patients, the expression of autophagy-related proteins was significantly elevated in in patients died after one to three weeks after the treatment. IL-1ß, IL-6, LC3-II and Beclin-1, but not Atg-5 values were significantly correlated with Scr. CONCLUSION: The expression of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients may change prominently after treatment with CRRT, so they are expected to be regarded as new prognostic indicators for AKI patients.

Frequency Shift Raman-Based Sensing of Serum MicroRNAs for Early Diagnosis and Discrimination of Primary Liver Cancers.

Frequency shift surface-enhanced Raman scattering (SERS) achieves multiplex microRNA sensing for early serological diagnosis of, and discrimination between, primary liver cancers in a patient cohort for whom only biopsy is effective clinically. Raman reporters microprinted on plasmonic substrates shift their vibrational frequencies upon biomarker binding with a dynamic range allowing direct, multiplex assay of serum microRNAs and the current best protein biomarker, α-fetoprotein. Benchmarking against current gold-standard polymerase chain reaction and chemiluminescence methods validates the assay. The work further establishes the frequency shift approach, sensing shifts in an intense SERS band, as a viable alternative to conventional SERS sensing which involves the more difficult task of resolving a peak above noise at ultralow analyte concentrations.

Immune memory at 17-years of follow-up of a single dose of live attenuated hepatitis A vaccine.

BACKGROUND: In recent years, hepatitis A virus (HAV) infection has declined considerably in China, associated with wide deployment of HAV vaccines and improvement in socio-economic indicators. Towards the elimination of HA in the country, we assessed the duration and characteristics of immunity conferred by the widely used, locally manufactured HAV vaccine. METHODS: This is a longitudinal cohort study that followed recipients of a live attenuated HAV vaccine 17 years after the initial administration. Blood samples were collected from participants pre- and two-week post-booster HAV vaccine dose. Serum anti-HAV antibody was measured by ELISA method. Memory B and T cells were determined by ELISPOT and Flow Cytometry assays, respectively. RESULTS: A robust anamnestic response was observed two-week post-challenge. Both HAV-specific memory B cell and T cells remained, and responded quickly when re-encountering HAV. The magnitude of recall responses was present, regardless of the status of the serum anti-HAV antibody pre-booster. CONCLUSIONS: We demonstrated long-term immunity from the live attenuated HAV vaccine, including antibody persistence and immunological memory. Considering the conditions that make elimination of infectious diseases feasible, following polio, hepatitis A could be targeted for elimination in China.

Variation analysis of norovirus among children with diarrhea in rural Hebei Province, north of China.

To understand the distribution of genotyping, as well as evolution of norovirus circulating among children<5yrs., a population-based diarrhea surveillance targeted children<5yrs. was conducted in rural Zhengding County, Hebei Province, China between October 2011 and March 2012. RT-PCR was used to amplify the capsid-encoding region of GI and GII norovirus to identify norovirus infection. All PCR products were sequenced and analyzed for genotyping and constructing phylogenetic tree. Dynamic distribution network was constructed by TempNet to illustrate the genetic relationships at two different time points. Bayesian evolutionary inference techniques were applied by BEAST software to study the norovirus evolution rate. During the 6-month surveillance period, 1091 episodes of diarrhea were reported from 5633 children under 5years of age lived in catchment area. 115 of 1091 stool specimens were detected as norovirus positive (10.54%). Five genotypes based on capsid gene sequences were identified, including GII.2 (11), GII.3 (52), GII.4 (47), GII.6 (4) and GII.7 (1). An identical haplotype of GII.4 circulated between 2006 and 2011 in Hebei Province. A mean rate of 6.29×10-2 nucleotide substitutions/site/year (s/s/y) was obtained for GII.3 viruses in Hebei, while the GII.4 viruses evolved at a mean rate of 3.67×10-2s/s/y. In conclusions, GII.3 (45.22%) and GII. 4(40.87%) are the predominant strain in Hebei Province in the winter season of 2011 and 2012. Different from the current consensus, our study shows that GII.3 noroviruses in Hebei Province evolved at a faster rate than GII.4 viruses.

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.