Jiang Wu

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 Unions 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.

Surveillance of Macrolide-Resistant Mycoplasma pneumoniae in Beijing, China, from 2008 to 2012

ABSTRACT Macrolide resistance rates of Mycoplasma pneumoniae in the Beijing population were as high as 68.9%, 90.0%, 98.4%, 95.4%, and 97.0% in the years 2008 to 2012, respectively. Common macrolide-resistant mobile genetic elements were not detected with any isolate. These macrolide-resistant isolates came from multiple clones rather than the same clone. No massive aggregation of a particular clone was found in a specific period.

Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans.

A randomized clinical trial was conducted to assess whether the immunogenicity of seasonal and pandemic (H1N1/09) influenza vaccines is affected by the order of vaccine administration. 151 healthy adult volunteers were randomized into three groups. All groups received one dose (15 μg haemagglutinin) each of a pandemic H1N1 vaccine and a seasonal trivalent vaccine. Group 1 received the pandemic H1N1 vaccine first, followed by the seasonal vaccine 21 days later. Group 2 received vaccinations in vice versa and Group 3 received both vaccines simultaneously. Post-vaccination blood samples were collected to determine the immunogenicity by hemagglutination-inhibition (HI), microneutralization (MN), and B cell ELISPOT assays. All three vaccination strategies were well-tolerated and generated specific immune responses. However, we found a significant difference in magnitude of antibody responses to pandemic H1N1 between the three groups. Pre- or co-vaccination with the seasonal flu vaccine led to a significant reduction by 50% in HI titre to pandemic H1N1 virus after pandemic vaccination. Pre- or co-vaccination of pandemic H1N1 vaccine had no effect on seasonal flu vaccination. MN and ELISPOT assays showed a similar effect. Vaccination with pandemic H1N1 vaccine first is recommended to avoid an associated inhibitory effect by the seasonal trivalent flu vaccine.

Multiple-Locus Variable-Number Tandem-Repeat Analysis of 201 Mycoplasma pneumoniae Isolates from Beijing, China, from 2008 to 2011

ABSTRACT A total of 201 Mycoplasma pneumoniae clinical isolates from Beijing, China, isolated from 2008 to 2011, were clustered into 16 multiple-locus variable-number tandem-repeat analysis (MLVA) types, of which 6 new MLVA types have never been reported previously. Type 1 isolates based on p1 gene genotyping were mainly MLVA types E, J, P, U, and X. There was no correlation between macrolide-resistant Mycoplasma pneumoniae and their MLVA type.

A Rapid Immune Response to 2009 Influenza A(H1N1) Vaccines in Adults: A Randomized, Double-Blind, Controlled Trial

A double-blind, randomized, controlled trial involving 706 adults was conducted to evaluate the immunogenicity and safety of different dosages of whole-virion or split-virion H1N1 influenza vaccines with or without aluminum adjuvant. A rapid and strong immune response was induced at day 14 after the first injection. The seroprotection rates ranged from 72.7% (95% confidence interval [CI], 62.7%-81.1%) for 5-microg whole-virion aluminum formulation to 97.0% (95% CI, 90.9%-99.7%) for 30-microg split-virion nonaluminum formulation. All formulations were well tolerated. The incidences of mild, moderate, and severe reactions were 71 (10.1%), 15 (2.1%), and 1 (0.1%) of 706 reactions, respectively. The 15-microg split-virion formulation had the best immunogenicity and safety.

The free vaccination policy of influenza in Beijing, China: The vaccine coverage and its associated factors

BACKGROUND In order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing. METHODS A cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information. RESULTS The influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801-3.655, P<0.010) times greater than that in urban areas. Different mechanisms of health education and health promotion have different influences on vaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR]=1.403, P<0.010; OR=1.812, P<0.010; OR=2.647, P<0.010). CONCLUSION The influenza vaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural-urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations, especially with a focus on expanding these efforts in urban areas.

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

OBJECTIVE Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. METHODS An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. FINDINGS 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. INTERPRETATION The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 microg dose induced immune response complying with European Union licensure criteria.

Immunogenicity and safety of three 2010–2011 seasonal trivalent influenza vaccines in Chinese toddlers, children and older adults: A double-blind and randomized trial

The 2009 influenza A(H1N1) pandemic strain was for the first time included in the 2010–2011 seasonal trivalent influenza vaccine (TIV). We conducted a double-blind, randomized trial in Chinese population to assess the immunogenicity and safety of the 2010–2011 TIV manufactured by GlaxoSmithKline and compared it with the counterpart vaccines manufactured by Sanofi Pasteur and Sinovac Biotech. Healthy toddlers (6–36 mo), children (6–12 y) and older adults (≥60 y) with 300 participants in each age group were enrolled to randomly receive two doses (toddlers, 28 d apart) or one dose (children and older adults). The immunogenicity was assessed by hemagglutination-inhibition (HI) assay. The solicited injection-site and systemic adverse events (AEs) were collected within 7 d after vaccination. All the three TIVs were well-tolerated with 15.1% of participants reporting AEs, most of which were mild. No serious AEs and unusual AEs were reported. Fever and pain were the most common systemic and injection-site AEs, respectively. The three TIVs showed good immunogenicity. The seroprotection rates against both H1N1 and H3N2 strains were more than 87% in toddlers after two doses and more than 95% in children and more than 86% in older adults after one dose. The seroprotection rates against B strain were 68–71% in toddlers after two doses, 70–74% in children and 69–72% in older adults after one dose. In conclusion, the three 2010–2011 TIVs had good immunogenicity and safety in Chinese toddlers, children and older adults and were generally comparable in immunogenicity and reactogenicity.

Changing epidemiological characteristics of Hepatitis A and warning of Anti-HAV immunity in Beijing, China: a comparison of prevalence from 1990 to 2017

ABSTRACT Backgroud: Beijing was hyper-endemic for hepatitis A until the 1990s and has been vaccinating against hepatitis A since 1994. The objective is to study the epidemiology and changes of antibody level of hepatitis A from 1990 to 2017. Methods: A multistage randomized cluster sampling serological cross-sectional study was conducted in individuals over one year old in 1992, 2006 and 2014 in Beijing. Venous blood samples were collected to test anti-HAV antibody. The incidence data of hepatitis A were obtained from National Notifiable Disease Reporting System (NNDRS) and CDC statistics in Beijing. The vaccination data of hepatitis A immunization were acquired from Beijing Immune Information System. Results: From 1990 to 2017, the reported incidence rate of HAV in Beijing declined from 59.41/100,000 in 1990 to 0.80/100,000 in 2017. The average age of HAV infection was postponed from individuals under 20 years old to individuals over 20 years old. After hepatitis A vaccine was introduced to Beijing, the outbreak of hepatitis A decreased sharply. Adjusted anti-HAV positive rate in general population was 68.23%, 81.73% and 82.47% respectively in 1992, 2006 and 2014. Due to hepatitis A vaccination conducted in children, the anti-HAV positive rate in individuals under 20 years old increased from 1992 to 2014, while in individuals over 20, this rate was barely changed. The coverage rate in target population was higher than 99% after hepatitis A vaccine was integrated into Expanded Program on Immunization (EPI). Conclusion: Incidence rate of hepatitis A in Beijing has decreased dramatically from 1990 to 2017. Hepatitis A vaccine plays an important role in protecting individuals under 20 years old. A higher proportion of adults will be susceptible to hepatitis A virus due to the decay of antibodies as they grow up from childhood to adulthood, which may result in possible outbreak of hepatitis A.