[Immunogenicity and safety of DTaP-IPV//PRP-T combined vaccine in infants in China].

OBJECTIVE: The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine. METHODS: Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIM(TM)) vaccinated at 2, 3, 4 months of age or 3, 4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIB(TM)) and IPV (IMOVAX PolioTM(TM)) vaccines vaccinated at 3, 4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection/seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines. RESULTS: The non-inferiority of DTaP-IPV//PRP-T combined vaccine vaccinated at 2, 3, 4 or 3, 4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsolicited severe adverse reactions was very low and similar to the control vaccines. CONCLUSION: DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines.

Antibody persistence at 18-20 months of age and safety and immunogenicity of a booster dose of a combined DTaP-IPV//PRP∼T vaccine compared to separate vaccines (DTaP, PRP∼T and IPV) following primary vaccination of healthy infants in the People's Republic of China.

This study assessed the antibody persistence, and the immunogenicity and safety of a booster dose of a DTaP-IPV//PRP∼T (Pentaxim®, Sanofi Pasteur's AcXim family) combined vaccine and of standalone vaccines one year after primary vaccination in the People's Republic of China. Participants (N=719) previously primed with DTaP-IPV//PRP∼T at 2, 3, 4 months (Group A, N=255), 3, 4, 5 months (Group B, N=233), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib®) and IPV (Imovax® Polio) at 3, 4, 5 months (Group C, N=231) received boosters of the same vaccines at 18-20 months of age. Seroprotection (SP) and seroconversion (SC) were determined before and 1 month after the booster. Safety was monitored from parental reports. In all groups 87.6-100% of participants had pre-booster protective anti-PRP, -diphtheria, -tetanus and -poliovirus antibody titers; post-booster, all SP rates were 100% and SC was ≥ 80.4% for anti-pertussis titers ≥ 4-fold increase. Reactogenicity was low for each group. These data support the use of the DTaP-IPV//PRP∼T vaccine in the People's Republic of China compared to separate DTaP, IPV, and PRP∼T administration in terms of both safety and immunogenicity.

Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.

The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

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.

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.

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.

[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.

A novel influenza A (H1N1) vaccine in various age groups.

BACKGROUND: There is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus. METHODS: A split-virus, inactivated candidate vaccine against the 2009 H1N1 virus was manufactured, and we evaluated its safety and immunogenicity in a randomized clinical trial. Subjects were between 3 and 77 years of age, stratified into four age groups. The immunization schedule consisted of two vaccinations, 21 days apart. Subjects were injected with placebo or with vaccine, with or without alum adjuvant, at doses of 7.5 microg, 15 microg, or 30 microg. Serologic analysis was performed at baseline and on days 21 and 35. RESULTS: A total of 2200 subjects received one dose, and 2103 (95.6%) received the second dose, of vaccine or placebo. No severe adverse side effects associated with the vaccine were noted. In the nonadjuvanted-vaccine groups, injection-site or systemic reactions, most mild in nature, were noted in 5.5 to 15.9% of subjects. Among the subjects receiving 15 microg of nonadjuvanted vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between 12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects 61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%, 97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine, with or without adjuvant. Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant. CONCLUSIONS: These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age. Lesser immune responses were seen after a single dose of vaccine in younger and older subjects. (ClinicalTrials.gov number, NCT00975572).

Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.

BACKGROUND: Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines. METHODS: A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays. RESULTS: All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively. CONCLUSIONS: The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00535665.

Antibody persistence after 2-dose priming and booster response to a third dose of an inactivated, adjuvanted, whole-virion H5N1 vaccine.

An inactivated, alum-adjuvanted, whole-virion H5N1 vaccine had been evaluated previously. Hemagglutination inhibition (HI) assays showed that the antibody levels declined significantly, with 4.8%-20.8% and 0%-18.8% of participants retaining seroprotection (HI titer >or=1:40) 6 and 12 months after the second dose, respectively. A third dose of the same vaccine given 12 months after the second dose significantly boosted immune responses. Thirty days after the third dose in the 1.25-, 2.5-, 5-, and 10-microg dose groups, 29.4%, 31.3%, 78.6%, and 90.0% of participants had HI titers >or=1:40, and 52.9%, 81.2%, 92.9%, and 100% of participants had microneutralization titers >or=1:40, respectively. Both the 5-microg and 10-microg doses met European Union criteria.

[Analysis and evaluation on quality of live attenuated measles vaccine from market surveillance sampling].

OBJECTIVE: To ensure the quality of live attenuated measles vaccine on the market, viral titers were determined as the market surveillance test. METHODS: The measles vaccine was sampled from sites located in 24 provinces (cities, autonomous regions) of China, including provincial CDC, municipal CDC, county CDC, and primary users. The virus titer of samples was tested to evaluate the quality status of measles vaccine on the market. RESULTS: For all the 54 lots of measles vaccine sampled in this study, the virus titers were in compliance with the requirements of the China Pharmacopeia Vol. III (2005 edition). In comparison with the original test results provided by the manufacturers, the mean virus titer was decreased 0.2 lg +/- 0.3. CONCLUSION: Viral titers of measles vaccine batches sampled from the market were all in compliance with the requirements of the China Pharmacopeia Vol. III (2005 edition). It showed that the measles vaccine in China market has good stability, and the cold chain system for measles vaccine conveyance and storage could ensure the vaccine efficacy.

[Study on the safety and immunogenicity of MF59-adjuvanted influenza subunit vaccine in Chinese elderly].

OBJECTIVE: To compare the safety and immunogenicity between a MF59-adjuvanted influenza subunit vaccine and a conventional non-adjuvanted influenza subunit vaccine. METHODS: A randomized, blind-designed controlled study was carried out, with 600 subjects (> or = 60 years of age) received MF59-adjuvanted influenza subunit vaccine (FLUAD, n = 400) or conventional non-adjuvanted influenza subunit vaccine (Agrippal, n = 200) respectively. The local and systemic reactions were observed on 0-7 days after vaccination. Haemagglutination inhibition (HI) titers of pre-and post-vaccination were detected by the HI assay. Seroconversion (4-fold increase) rate of subjects was calculated using baseline data when it was under naive level, and the protection rate when HI titer achieving the level of protection (> or = 1:40) after vaccination. Geometric mean titer (GMT) and its increasing folds were calculated. Differences between safety and immunogenicity were also calculated. RESULTS: The local and systemic reaction rates were similar between both groups, but the duration in injection site was frequent for Agrippal (P < 0.05), while mild pain and fever in injection site were frequent for FLUAD. On immunogenicity test, for those subjects whose baseline was under naive level while the seroconversion rate against A/H3N2 viral strain after vaccination--FLUAD was significantly higher than Agrippal (P < 0.001). Aside from A/H1N1 viral strain, the rate of protection on both groups were significantly higher than those from baseline data, but for A/H3N2 viral strain, FLUAD was significantly higher than Agrippal (P < 0.001). GMT was higher than baseline (P < 0.001) after both groups being vaccinated but FLUAD group was significantly higher than Agrippal group. CONCLUSION: FLUAD was well tolerated by Chinese elderly and its immunogenicity level induced by FLUAD was higher than that of Agrippal, showing that it would benefit the elderly with hypoimmunity.

[Evaluation on the safety and immunogenicity of Canada split influenza virus vaccine].

OBJECTIVE: To evaluate the safety and immunogenicity of Canada split influenza virus vaccine. METHODS: Cluster samples were by randomly chosen and divided into split vaccination group and homoimported influenza vaccination group. RESULTS: After injection, fever-reaction and local reaction rates of 'trial' group were found as 3.69% and 1.75% respectively, but no statistical significance was found when compared with 'control' group. However the antibody positive rates of 'trail' and 'control' groupsappeared statistically significant (H1N1: 96.8% vs. 92.3%, H3N2: 95.8% vs. 90.2%, B: 52.3% vs. 62.3%). For geometric mean titer (GMT) of type H1N1, H3H2 and B antibody, 'trial' group and 'control' group increased 22.4, 16.8, 8.2 and 21.2, 12.5 and 7.4 times respectively. The antibody protective rates of type H1N1, H3N2 and B were 99%, 99% and 53.9% for 'trial' group, and 96.2%, 98.4% and 62.3% for 'control' but with no statistically significant difference. CONCLUSION: Influenza split vaccine made in Shire company in Canada was safe and with good immunogenicity.

[Safety and immunogenicity of split vaccines of influenza viruses].

OBJECTIVE: To evaluate the safety and immunogenicity of influenza split vaccine. METHODS: According to the criteria of No.2002SL0043, instruction of application for new drug in clinical trial issued by the State Food and Drug Administration, 876 healthy persons were divided at random into vaccine group and control group. The trial was performed with the double blind method. Local and systemic adverse reactions were observed within 3 days after the vaccine group subjects were vaccinated. The antibody response to vaccines was detected with hemagglutination inhibition (HI) test. Numbers of seroconversions and HI titers greater than or equal to 40, as well as the mean geometric titer increase in HI were analyzed. RESULTS: There was no significant difference in local and systemic adverse reaction between vaccine and control groups. Meanwhile there was also no significant difference in seroconversions and protective level between two groups. However, there was obvious difference in mean geometric titer increase of antibody against H1N1 virus, while there was no significant difference in that of antibodies to H3N2 and type B viruses. CONCLUSIONS: The safety and immunogenicity of both vaccines are excellent.