Safety and Viral Shedding of Live Attenuated Influenza Vaccine (LAIV) in Chinese Healthy Juveniles and Adults: A Phase â Randomized, Double-Blind, Placebo-Controlled Study.

This study was a randomized, double-blind, placebo-controlled study to evaluate the safety and viral shedding of live attenuated influenza vaccine (LAIV) in Chinese healthy juveniles and adults. A total of 80 Eligible volunteers were divided into two age groups (≥18 and 3-17 years old). Volunteers were randomly and equally assigned to the experimental group and placebo-controlled group by ratio of 3:1 in each age group. Vaccination was carried out in steps. Totally, 34 (56.67%) adverse events and 24 (40.00%) adverse reactions of the LAIV group were reported. Most adverse reactions were grade 1 and grade 2, and the incidence of adverse reactions that grade 3 was 5%. The most common local reaction was runny nose/nasal congestion (n = 4, 6.67%). And the most common general reaction was fever (n = 10, 16.67%). There were no statistically significant differences in the incidence of total adverse reactions, different grades of adverse reactions, and symptoms between the experimental group and placebo-controlled group. No severe adverse events were reported. Three subjects (5.00%) had been detected vaccine strains on the 3rd day after LAIV vaccination; one was type B and the other two were H3N2. Four subjects (6.67%) had been detected with vaccine strains on the 7th day after LAIV vaccination, all were H3N2. There were no subjects detected carrying the influenza virus on the 15th day after vaccination. There were no statistically significant differences in the positive rate of vaccine strains of influenza virus between the experimental group and placebo-controlled group. The vaccine was well tolerated and not associated with increased rates in adverse reactions or the occurrence of severe adverse events. Pathogenicity of shed vaccine virus to surrounding people was not observed. Thus, Phase Ⅱ study can be carried out as scheduled.

Neutralizing antibody activity, safety and immunogenicity of human anti-rabies virus monoclonal antibody (Ormutivimab) in Chinese healthy adults: A phase â ¡b randomized, double-blind, parallel-controlled study.

OBJECTIVE: This study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults. METHODS: Subjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days. RESULTS: A total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT. All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %). CONCLUSION: Compared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group. REGISTRATION: ClinicalTrials.gov #NCT02559921.

Population Pharmacodynamic Analyses of Human Anti-Rabies Virus Monoclonal Antibody (Ormutivimab) in Healthy Adult Subjects.

Ormutivimab is the first recombinant human anti-rabies monoclonal antibody (rhRIG) approved for clinical application in China. In this study, a population pharmacodynamic (PPD) model was established to compare the neutralizing antibody activities of Ormutivimab and human rabies immunoglobulin (HRIG), alone or combined with human rabies vaccine (Vero), in a phase II clinical trial, and to recommend a target dose for the phase III trial. The model was verified to fit the PPD data well. The stability of the model was verified by the bootstrap method. The level of neutralizing antibodies in vivo increased rapidly after administration of Ormutivimab or HRIG. Neutralizing antibodies with a strong activity were produced at 7 days (Ormutivimab + vaccine) or 10 days (HRIG + vaccine) after induction by the vaccine in vivo. Compared to that induced by HRIG + vaccine, the level of the neutralizing antibodies induced by Ormutivimab + vaccine peaked higher and faster. The levels of neutralizing antibodies induced by Ormutivimab + vaccine and HRIG + vaccine were similar within 21 days after administration. According to these results and the safety data, 20 IU·kg-1 was recommended as the target dose in the confirmatory study of Ormutivimab. Registration: ClinicalTrials.gov #NCT02559921.

Safety and immunogenicity of a quadrivalent, inactivated, split-virion influenza vaccine (IIV4-W) in healthy people aged 3-60 years: a phase III randomized clinical noninferiority trial.

BACKGROUND: A quadrivalent split influenza vaccine IIV4-W against both influenza A and B viruses is urgently needed. METHODS: To evaluate the safety and immunogenicity of IIV4-W in people aged 3-60 years, 2400 participants recruited in a double-blind phase III trial and were randomly assigned to the IIV4-W, TIV1 and TIV2 groups. The immunogenicity indicators were measured at 28 days postvaccination and for 180 days for safety follow-up. RESULTS: Adverse events (AEs) occurred in 162 (20.28%), 116 (14.55%) and 123 (15.41%) participants in the IIV4-W, TIV1 and TIV2 groups, respectively. All these AEs were mild and self-limiting, and no serious AEs related to the vaccines were observed. IIV4-W elicited a non-inferior immune response for matched strains (the lower limit of 95% CI for GMT ratio >0.67, for SCR and SPR difference >-10%) and superior immune response for the additional B strains (the lower limit of 95% CI for GMT ratio >1.5, for SCR difference >10%) versus TIVs. The lower limit of the 95% confidence interval of the GMT increase fold, the seroconversion rate and the seroprotection rate exceeded 2.5, 40% and 70% for the four strains in IIV4-W respectively. CONCLUSIONS: IIV4-W was noninferior to the TIV-matched strains and was superior to the additional B strain. IIV4-W was safe in the participants and elicited high antibody titers.

Safety of two doses of an inactivated hepatitis a vaccine given 6 months apart in healthy toddlers, children, and adolescents aged 12 months to 15 years in China: a phase IV study.

Hepatitis A is a vaccine-preventable infection caused by the HA virus (HAV) with transitional to intermediate endemicity in China. An inactivated vaccine first licensed in China in 2010 (Avaxim® 80U Pediatric) is indicated for primary and booster vaccination in children from 12 months to 15 years of age. This Phase IV, open-label, single-arm trial supported licensure in pediatric age groups in China. A total of 355 healthy infants and toddlers (< 2 years of age), children (2 to 11 years of age), and adolescents (≥ 12 years of age) were enrolled to receive two doses of intramuscular HA vaccine, separated by 6 months. Participants were split into Group 1 (infants and toddlers: N = 270) and Group 2 (children and adolescents: N = 85). Safety was assessed by solicited injection site and systemic adverse events (AEs) for 7 days and unsolicited AEs for 30 days after each vaccination. Serious AEs (SAEs) were collected throughout. Immunogenicity was not assessed. Analyses were descriptive. Both vaccinations were very well tolerated in each group. The incidence of solicited injection site reactions was lower in Group 1 (17.9%) than Group 2 (33.3%) and for solicited systemic reactions was similar for each group. The incidence of unsolicited AEs in Group 1 was 6.3% and none in Group 2. For solicited and unsolicited AEs the incidence was slightly higher after the first vaccination. There were no SAEs. Overall, the good safety profile of this pediatric HA vaccine was confirmed in infants, toddlers, children, and adolescents aged 12 months to 15 years in China.

Analysis of risk factors for persistent infection of asymptomatic women with high-risk human papilloma virus.

OBJECTIVE: This study aims to prevent persistentinfection, reduce the incidence of cervical cancer, and improve women's health by understanding the theoretical basis of the risk factors for continuous infection of asymptomatic women with high-risk human papilloma virus (HPV) strains via information collected, which includes the persistent infection rate and the most prevalent HPV strain types of high risk to asymptomatic women in the high-risk area of cervical cancer in Linfen, Shanxi Province. METHODS: Based on the method of cluster sampling, locations were chosen from the industrial county and agricultural county of Linfen, Shanxi Province, namely the Xiangfen and Quwo counties. Use of the convenience sampling (CS) method enables the identification of women who have sex but without symptoms of abnormal cervix for analyzing risk factors of HPV-DNA detection and performing a retrospective questionnaire survey in these 2 counties. Firstly, cervical exfoliated cell samples were collected for thin-layer liquid-based cytology test (TCT), and simultaneously testing high-risk type HPV DNA, then samples with positive testing results were retested to identify the infected HPV types. The 6-month period of testing was done to derive the 6-month persistent infection rate. The retrospective survey included concepts addressed in the questionnaire: basic situation of the research objects, menstrual history, marital status, pregnancy history, sexual habits and other aspects. The questionnaire was divided into a case group and a comparison group, which are based on the high-risk HPV-DNA testing result to ascertain whether or not there is persistent infection. Statistical analysis employed Epidate3.1 software for date entry, SPSS17.0 for date statistical analysis. Select statistic charts, Chi-Square Analysis, single-factor analysis and multivariate Logistic regression analysis to analyze the protective factors and risk factors of high-risk HPV infection. Risk factors are predicted by using the classification tree. RESULTS: 3000 women participated in the study. The high-risk type HPV infection rate was 8.7%, the persistent infection rate was 7.5%. The persistent infection rates for the 2 age groups (ages 18-26 and 27-30) were 6.9% and 8.7%. The persistent infection rates of Xiangfen county were 7.4% and 7.4% respectively, and those of Quwo county were 7.8% and 11.6% respectively; there was no significant difference between each pair of groups. Single risk-factor analysis showed that first-time sex at age under 20, high school/technical secondary school education or above, multiple sexual partners, having more than 2 sexual partners in the past 6 months, oral sex, and colitis are the risk factors of high-risk type HPV infection. Multivariate analysis showed that the number of sexual partners, smoking and oral sex had an effect on HPV infection. The risk of HPV infection from smoking was 5.0-fold higher, and the risk of HPV infection from oral sex was 6.1-fold higher. Having more than 2 sexual partners increase the risk of HPV infection. By the predicated model analysis, the probability of HPV conveyed by oral sex was 14.8%; if the sexual companion number was zero or more than 2 without oral sex, the probability of HPV infection was 12.1%; if there was one sexual partner who smokes without oral sex, the probability of infection was 18.6%; if there was one sexual partner who does not smoke and without oral sex, the probability of infection was 3.6%. CONCLUSION: The persistent infection rate of asymptomatic women for high-risk type HPV is lower than those women in all ages. High-risk type HPV infection risk factors include the number of sexual partners, oral sex and smoking. Thus, young women may be able to reduce the risk of infection with high-risk type HPV by reducing the number of sexual partners, forming a correct sexual life habit, and avoiding smoking.

Immunogenicity and safety of purified vero cell rabies vaccine (PVRV) produced by Liaoning Cheng Da Co. under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese adults aged 50 and above.

BACKGROUND: Two kinds of regimens (2-1-1 and 1-1-1-1-1) can be selected after Zagreb regimen(2-1-1)of PVRV was officially approved in Beijing in January 2015. Up to now, the subjects for most studies about the comparison between Zagreb and Essen regimen are under 50 y old, rarely at and above. Aging of the immune system may result in decreasing efficacy of vaccination, especially for adults aged above 65-70 y. This study compared the safety and immunogenicity of the Zagreb and Essen regimen in Chinese adults aged 50 and above with the goal to provide a supplemental data for this age group. METHODS: A total of 114 cases were divided into 2 groups randomly, received PVRV under the Zagreb and Essen regimens respectively. Serum samples were collected at D0, D7, D14, D42, D180 and D365 to determine the rabies serum neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT). Safety analyses were made by comparing the AEs in day-3, day-7, and day-(7 + 21) in Zagreb or day-(7 + 28) in Essen by gender and age cohorts. RESULTS: 617 blood samples were obtained. Two groups showed similar immunogenicity, the neutralizing antibody titer of all subjects at D14 and D42 showed >0.5 IU/ml. Under the same regimen, Subjects ≥65 y had lower GMC than those who <65 years from D7 to D365 within 2 groups. This difference was significantly shown on D7, D14, D180 in Zagreb group, and on D180 in Essen group (t = 2.38, p = 0.02; t = 3.78, p < 0.001; t = 2.30, p = 0.03; t = 4.42, p < 0.001). Subjects<65 years had higher seroconversion rate compared to ≥65 y on D7, D180 and D365 in both 2 groups, this difference was also significantly shown on D180, D365 in Zagreb group and on D180 in Essen group (χ2 = 20.66, p < 0.001; χ2 = 6.56, p = 0.02; χ2 = 10.96, p = 0.002). Two regimens all showed favorable performances with mildly or common adverse events (AEs). The incidence of local AEs after 3 d in Essen group was higher than Zagreb group (χ2 = 9.69, p = 0.002). The most common local AE was pain, the incidences (8.8%) in Zagreb group was higher than Essen group (8.4%, χ2 = 5.12, p = 0.02). All AEs for Zagreb group and 52.3% of AEs for Essen group occurred during the first 72 hours. During the first 72 hours, subjects aged <65 in Zagreb group (16.26%) had higher incidences of AEs than Essen group (8.57%, χ2 = 4.54, p = 0.03), males in Zagreb group (16.05%) had higher incidence of AEs than Essen group (5.71%, χ2 = 5.34, p = 0.02). The incidences of AEs close in during the first 7 d. CONCLUSION: The Zagreb and Essen regimens demonstrated the similar safety and efficacy of PVRV in Chinese adults aged 50 and above. People ≥65 y showed reduced immune response to both regimens. More AEs for the Zagreb regimen were observed within the first 72 hours, especially for male and people < 65 y.

2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study.

BACKGROUND: This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine. METHOD: In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years. RESULTS: Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P < .0001), and the vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P < .0001). Geometric mean titers of neutralizing antibody in participants remained high during the 2-year follow-up period, and no vaccine-related serious adverse events were recorded. CONCLUSIONS: Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children. CLINICAL TRIALS REGISTRATION: NCT01508247.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

AIM: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. METHODS: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). RESULTS: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. CONCLUSIONS: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Immunological persistence of a seasonal influenza vaccine in people more than 3 years old.

To evaluate antibody persistence of Aleph inactivated split influenza vaccine, 3308 healthy Chinese people more than 3 years old were enrolled in a hemagglutination inhibition (HI) assay before vaccination, 641 were screened by HI assay negative, 437 of which received one dose of Aleph inactivated split influenza vaccine and 204 of which received one dose of control vaccine (recombinant hepatitis B). After vaccination, the receivers were collected blood at 1st month, 3rd month, 6th month and 12th month for Aleh influenza vaccine antibody persistence assess. The antibody test were determined by hemagglutination inhibition (HI) assay. There were significant difference in antibody geometric mean titer between experimental group and control at 1st month and 3rd month after vaccination. Influenza antibody could persist at least up to 3rd month. Because of the local spring influenza epidemic, we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination. Influenza viruses are important human respiratory pathogens. Immunization is widely acknowledged to currently be the most effective method of minimizing the impact of pandemic influenza. Through we have checked many references about Influenza vaccine, the duration of protective antibody for influenza vaccines are still not available. Based on this situation and our previous work, (11) Influenza vaccine antibody duration analyze are necessary. This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009(H1N1), A/Peth/16/2009(H3N2) strain and B/Brisbane/60/2008. 641 were screened from 3302 volunteers by HI test of influenza A and confirmed enrollment based on the antibodies titer less than 1:10. After administered with one dose of Aleph influenza vaccine, blood samples were collected. 437 subjects (3-10 y: 131; 11-17 y: 110; 18-54 y: 69; ≥ 55 y: 127) were vaccinated influenza vaccine as test group. 204 subjects (3-10 y: 70; 11-17 y: 47; 18-54 y: 28; ≥ 55 y: 59) were vaccinated recombinant hepatitis B vaccine as control group. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. The persistence of HI immune response against the vaccine strain was assessed through GMT. The immunogenicity of the Aleph influenza vaccine induced all reached the standards at 1st month and GMTs peak could persist at least up to 3rd month. (This study has been registered at clinicaltrials.gov under registration no. NCT01758185.). Because of the local spring influenza epidemic we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination.

A randomized, controlled, blinded study of the safety, immunogenicity and batch consistency of Aleph inactivated split influenza vaccine made in China in Chinese people.

To evaluate the safety, immunogenicity and batch consistency of Aleph inactivated split influenza vaccine, 3308 healthy Chinese people more than 3 years old were enrolled in a randomized, controlled, blinded study and divided into four age groups: 3-10 years, 11-17 years, 18-54 years, and more than 55 years. Each age group was then randomized (2:1) to receive either influenza vaccine or control vaccine (recombinant hepatitis B) for one dose. Also each influenza vaccine group was randomized (1:1:1) to receive three different batches of influenza vaccine. Systematic and local adverse reactions for 28 days after vaccination were recorded, and influenza antibody titer was determined by hemagglutination inhibition (HI) assay at 28 days after vaccination. There were significant differences in seroconversion and seroprotection rates achieved post-immunization of three strains of influenza antibody (H1N1, H3N2, B) between experimental group and control group in all age groups (P<0.05). In addition, there were no statistically significant differences in local and systematic reaction rates after vaccination between the experimental and control group in all age groups (P>0.05), except for the systematic reaction rates in the 18-54 years and ≥ 55 years age groups (P<0.05). Thus, Aleph inactivated split influenza vaccine has good safety and immunogenicity.

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.

A randomized, controlled, blinded study of the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine injected at different intramuscular sites in Chinese infants.

To compare the safety and immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccine administered via the vastus lateralis and deltoid muscles, 320 healthy Chinese infants<12 mo of age were enrolled in a randomized, controlled, blinded study and divided into 2 age groups: 2-5 mo and 6-12 mo. Each age group was then randomized (1:1) to either the vastus lateralis (experimental) group who received Hib vaccination into this muscle 2 or 3 times at monthly intervals, or the deltoid (control) group who received Hib vaccination into this muscle either 3 times (2-5 mo group) or twice (6-12 mo group) at monthly intervals. Local and systemic adverse reactions after each vaccine dose were recorded, and Hib-PRP antibody concentrations were determined by ELISA at 28 d after completion of the immunization schedule. There were no significant differences in the proportions of subjects with post-immunization Hib-PRP antibody concentrations ≥1.0 µg/mL or ≥0.15 µg/mL with the two injection sites for either age group, or in the post-immunization Hib-PRP antibody concentrations achieved (P>0.05). In addition, there were no significant differences in the rates of local and systemic reactions after the first and second vaccinations between the 2 injection sites for either age group (P>0.05), but the rate of systemic reactions in the 2-5 mo group after the third vaccination via the vastus lateralis muscle was significantly lower than after deltoid vaccination (0% vs 8.57%; P<0.05). Thus, administration via the vastus lateralis muscle is worth considering for Hib vaccination.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

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.

[Analysis of safety and effects on the oral whole cell/recombinant B subunit cholera vaccine in university students and workers].

OBJECTIVE: To evaluate the safety, immunogenicity and protective efficiency of the oral whole cell/recombinant B subunit cholera vaccine in Beijing Olympic volunteers and workers. METHOD: Analyzing the incidence rate of adverse reaction and Protective Rate (PR) after taking the vaccine in Olympic volunteers in 6 universities in Beijing; comparing the anti-cholera toxin (CT) detected with ELISA prior and after taking the vaccine in Olympic workers. RESULTS: The total rate of adverse reaction of Olympic volunteers was 0.38%; the main side effects were gastrointestinal symptoms, such as bellyache and diarrhea which were mild and temple; the acute diarrhea incidence rate of Olympic volunteers after taking the vaccine was significantly lower than those not taking it, the PR was 76.27%; the positive rate of anti-CT of Olympic workers after taking the vaccine was significantly higher than those before taking it, the levels of anti-CT titers declined after 6 months since they had taken the vaccine. CONCLUSION: The results from above two observed population indicate that the oral rBS-WC cholera vaccine is efficient and safe.