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1.
Hum Vaccin Immunother ; 12(12): 3072-3078, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27565435

RESUMO

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/administração & dosagem , Injeções Intramusculares , Masculino , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
2.
Vaccine ; 33(39): 5127-34, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26279339

RESUMO

BACKGROUND: The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. METHODS: Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. RESULTS: 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). CONCLUSIONS: Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated.


Assuntos
Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Austrália , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/normas , Feminino , Voluntários Saudáveis , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/normas , Adulto Jovem
3.
Vaccine ; 33(21): 2485-92, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25843270

RESUMO

BACKGROUND: Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. METHODS: This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. CONCLUSIONS: In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults. CLINICAL TRIAL REGISTRY NUMBER: NCT01481454.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Anticorpos Antivirais/sangue , Austrália , Criança , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/administração & dosagem , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Filipinas , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
4.
Lancet ; 384(9951): 1358-65, 2014 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-25018116

RESUMO

BACKGROUND: An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. METHODS: We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. FINDINGS: We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse events (402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the vaccine group and 33 (1%) of those in the control group had serious adverse events that happened within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this age group and were mainly infections and injuries. INTERPRETATION: Our findings show that dengue vaccine is efficacious when given as three injections at months 0, 6, and 12 to children aged 2-14 years in endemic areas in Asia, and has a good safety profile. Vaccination could reduce the incidence of symptomatic infection and hospital admission and has the potential to provide an important public health benefit. FUNDING: Sanofi Pasteur.


Assuntos
Vacinas contra Dengue/administração & dosagem , Dengue/prevenção & controle , Adolescente , Criança , Pré-Escolar , Vacinas contra Dengue/efeitos adversos , Feminino , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Masculino , Resultado do Tratamento
5.
Pediatr Infect Dis J ; 33(6): 643-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24717964

RESUMO

BACKGROUND: The live, attenuated Japanese encephalitis (JE) chimeric virus vaccine (JE-CV) is licensed in Thailand and Australia for prophylaxis of JE in individuals at the age of 12 months. JE-CV has not yet been compared with the SA14-14-2 JE vaccine, which is also licensed in Thailand. METHODS: In this phase 3, observer-blinded trial, 300 children at the age of 9-18 months were randomized 1:1 to receive 1 dose of JE-CV or SA14-14-2. JE neutralizing antibody titers were assessed using PRNT50. The primary endpoint was the noninferiority of seroconversion against JE on Day 28 after JE-CV compared with SA14-14-2, as assessed using the 95% confidence interval of the difference between the groups. Safety and reactogenicity were described in each group using conventional methods, including the reporting of solicited and unsolicited adverse events. RESULTS: The seroconversion rate on Day 28 was 99.2% in each group. Noninferiority was demonstrated as the difference between the JE-CV and SA14-14-2 groups was -0.012 percentage points (95% confidence interval: -3.6 to 3.6), which was above the required -10%. The seroprotection rate remained very high at Month 6 and comparable between groups, but a slight decrease was observed in the JE-CV group between Months 6 and 12. Current recommendations for both vaccines call for a booster dose 12-24 months after primary immunization to maintain high seroprotection rates in the long term. Geometric mean titers (GMTs) on Day 28 after vaccination were 507 (1/dil) in the JE-CV group and 370 (1/dil) in the SA14-14-2 group, decreasing by 4.3-fold and 3.6-fold, respectively, to Month 6 before remaining stable to Month 12 and comparable between groups. Solicited reactions were all reported at lower rates after vaccination with JE-CV compared with SA14-14-2. CONCLUSIONS: A single dose of JE-CV elicited a noninferior immune response compared with SA14-14-2 and had a satisfactory safety profile.


Assuntos
Encefalite Japonesa/prevenção & controle , Vacinas contra Encefalite Japonesa/administração & dosagem , Adolescente , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Encefalite Japonesa/epidemiologia , Feminino , Humanos , Lactente , Vacinas contra Encefalite Japonesa/efeitos adversos , Vacinas contra Encefalite Japonesa/imunologia , Masculino , Tailândia/epidemiologia
6.
Vaccine ; 32(41): 5363-9, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24631095

RESUMO

BACKGROUND: Japanese encephalitis (JE) is the most important cause of viral encephalitis in Asia. METHODS: In this randomized, open-label, multicenter trial in 550 children aged 12 to 18 months in Taiwan, children received one dose of JE-CV and one dose of MMR vaccine. Vaccines were either administered separately 6 weeks apart (Groups 'JE-CV' and 'MMR', named after which vaccine was given first), or concomitantly (Group 'Co-Ad'). JE neutralizing antibody titers were assessed using PRNT50. MMR antibody levels were determined by ELISA. RESULTS: All groups had low seroprotection/seropositivity rates (<10%) before vaccination for all antigens. Forty two days after vaccination, on either Study Day 42 or 84, seroconversion rates for all antigens were high in all groups, irrespective of the order of vaccinations. Seroconversion for JE ranged from 96.9% in Group Co-Ad on D42 to 100% in Group MMR. Non-inferiority was demonstrated for all analyses as the lower bound of the 95% CI of the difference in seroconversion rates between groups was above the pre-defined limit of -10.0%. The immune responses remained high for all antigens and well above the level of protection 12 months after vaccination in all groups. There were no safety concerns. CONCLUSIONS: JE-CV is safe and induces a strong protective immune response which persists over 1 year when co-administered with MMR vaccine.


Assuntos
Formação de Anticorpos , Vacinas contra Encefalite Japonesa/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Encefalite Japonesa/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Sarampo/prevenção & controle , Caxumba/prevenção & controle , Rubéola (Sarampo Alemão)/prevenção & controle , Taiwan
7.
Vaccine ; 31(49): 5814-21, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24135573

RESUMO

BACKGROUND: Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. METHODS: In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. RESULTS: 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). CONCLUSIONS: This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia.


Assuntos
Vacinas contra Dengue/uso terapêutico , Dengue/prevenção & controle , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Proteção Cruzada , Vacinas contra Dengue/efeitos adversos , Feminino , Humanos , Imunidade Humoral , Esquemas de Imunização , Malásia , Masculino , Método Simples-Cego , Vacinação/efeitos adversos
8.
PLoS Negl Trop Dis ; 7(7): e2331, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23936565

RESUMO

BACKGROUND: Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed. METHODS AND PRINCIPAL FINDINGS: This prospective, multicenter, active fever surveillance, cohort study was conducted in selected centers in Indonesia, Malaysia, Philippines, Thailand and Vietnam to determine the incidence density of acute febrile episodes (≥ 38 °C for ≥ 2 days) in 1,500 healthy children aged 2-14 years, followed for a mean 237 days. Causes of fever were assessed by testing acute and convalescent sera from febrile participants for dengue, chikungunya, hepatitis A, influenza A, leptospirosis, rickettsia, and Salmonella Typhi. Overall, 289 participants had acute fever, an incidence density of 33.6 per 100 person-years (95% CI: 30.0; 37.8); 57% were IgM-positive for at least one of these diseases. The most common causes of fever by IgM ELISA were chikungunya (in 35.0% of in febrile participants) and S. Typhi (in 29.4%). The overall incidence density of dengue per 100 person-years was 3.4 by nonstructural protein 1 (NS1) antigen positivity (95% CI: 2.4; 4.8) and 7.3 (95% CI: 5.7; 9.2) by serology. Dengue was diagnosed in 11.4% (95% CI: 8.0; 15.7) and 23.9% (95% CI: 19.1; 29.2) of febrile participants by NS1 positivity and serology, respectively. Of the febrile episodes not clinically diagnosed as dengue, 5.3% were dengue-positive by NS1 antigen testing and 16.0% were dengue-positive by serology. CONCLUSIONS: During the study period, the most common identified causes of pediatric acute febrile illness among the seven tested for were chikungunya, S. Typhi and dengue. Not all dengue cases were clinically diagnosed; laboratory confirmation is essential to refine disease burden estimates.


Assuntos
Infecções Bacterianas/epidemiologia , Febre/epidemiologia , Febre/etiologia , Viroses/epidemiologia , Adolescente , Ásia/epidemiologia , Infecções Bacterianas/microbiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Viroses/virologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-23682437

RESUMO

We conducted a hospital-based study from June 2002 to December 2006 of Thai children aged 1-15 years with acute hepatic failure (AHF) to determine the causes and outcomes. Eleven children were included in the study. Hepatitis B virus was the cause of AHF in one child, infection-associated hemophagocytic syndrome was the cause in 1 child, Wilson's disease was the cause in 1 child and dengue fever was suspected to be the cause in 2 children. In 6 children the cause of AHF was unknown. Jaundice was reported in 9 of 11 children. Ten of 11 children had mild to moderate encephalopathy on admission. Five of 11 children died due to AHF. No liver transplantations were performed among the children in this study. Further studies into the relationship between dengue infection and AHF are needed.


Assuntos
Criança Hospitalizada/estatística & dados numéricos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/etiologia , Adolescente , Anticorpos Antivirais , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Falência Hepática Aguda/virologia , Masculino , Prognóstico , Tailândia/epidemiologia
10.
J Med Assoc Thai ; 94(8): 916-26, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21863672

RESUMO

OBJECTIVE: The present study (NCT00449670) in Asian subjects (18-60 years) evaluated the manufacturing consistency of four formulations of 3.75 mg AS03(A)-adjuvanted H5N1 influenza vaccine, in terms of post-immunization Hemagglutination Inhibition (HI) titers against the A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains. The immunogenicity and safety of the vaccine in the Thai population are reported herein. MATERIAL AND METHOD: Subjects were randomized (2:2:2:2.:1:1) between four vaccine groups and two control groups to receive two doses of either the AS03(A)-adjuvanted or non-adjuvanted H5N1 vaccine formulations, 21 days apart. Sera were assayed for HI antibody titers against the two strains. RESULTS: After the second dose of AS03(A)-adjuvanted vaccine, 94.2% subjects in the H5N1-AS03(A) groups seroconverted and 94.9% subjects were seroprotected against the A/Vietnam/1194/2004 strain. Cross-clade immune response against the A/Indonesia/05/2005 strain was observed. All vaccine formulations had an acceptable safety profile. CONCLUSION: This antigen-sparing AS03(A)-adjuvanted influenza vaccine could be a suitable candidate for combating and mitigating future influenza pandemics.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Vacinação , Adolescente , Adulto , Anticorpos Antivirais/sangue , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Esquemas de Imunização , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Tailândia , Adulto Jovem
11.
Hum Vaccin ; 7(1): 74-80, 2011 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-21228629

RESUMO

AIM: The lyophilized formulation of the human rotavirus vaccine, RIX4414 (RotarixTM), is recommended to be stored at 2°C-8°C for optimal immunogenicity. In some settings with inadequate infrastructure for vaccine storage, unforeseen circumstances may cause cold chain breakage, resulting in the vaccine to be left at ambient temperatures. This study evaluated the heat stability of lyophilized RIX4414 vaccine in terms of immunogenicity when stored at tropical room temperature (37 °C) for 7 days before reconstitution. RESULTS: There was no statistically significant difference detected between RIX4414 vaccine stored at 2 °C-8 °C (Group RIX4414_control, n = 171) and that stored at 37 °C for 7 days (Group RIX4414_37 °C, n = 47) in terms of seroconversion rate and vaccine take. The anti-rotavirus IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1%-90%) and 87.8% (95% CI: 73.8%-95.9%) in Groups RIX4414_control and RIX4414_37 °C, respectively. None of the 25 infants in placebo group seroconverted. The vaccine take in the respective vaccine groups were 88% (95% CI: 82.1%-92.5%) and 93.5% (95% CI: 82.1%-98.6%) and Geometric Mean Concentrations (GMCs) were 134.4 U/mL (95% CI: 104.5-172.9) and 163.7 U/mL (95% CI: 98.9-271.1). METHODS: Healthy infants aged 6-12 weeks, received two oral doses of either the RIX4414 vaccine stored at 2 °C-8 °C, RIX4414 vaccine stored at 37 °C for 7 days or placebo, according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus IgA antibody levels (cut off: ≥ 20 U/mL by ELISA), anti-rotavirus IgA antibody GMCs and vaccine take were calculated 2 months post-Dose 2. CONCLUSION: Lyophilized RIX4414 vaccine stored at 37°C for 7 days before reconstitution has similar immunogenicity as the vaccine stored at 2 °C-8 °C. These results supported the use of RIX4414 in settings where the vaccine might be exposed to higher than the recommended storage temperatures.


Assuntos
Armazenamento de Medicamentos/métodos , Vacinas contra Rotavirus/imunologia , Administração Oral , Anticorpos Antivirais/sangue , Estabilidade de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Lactente , Masculino , Placebos/administração & dosagem , Vacinas contra Rotavirus/administração & dosagem , Temperatura Ambiente , Fatores de Tempo , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
12.
Hum Vaccin ; 6(3)2010 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-20220306

RESUMO

AIM: The lyophilized form of the human rotavirus RIX4414 vaccine (Rotarix()) is usually reconstituted with a liquid calcium carbonate (CaCO(3)) buffer and administered orally. However, errors in the reconstitution could occur (e.g. reconstituted with water instead of CaCO(3) buffer) or the buffer might be temporarily unavailable in few instances. This study was conducted to evaluate the immunogenicity of the RIX4414 vaccine if the vaccine was reconstituted with other agents (e.g., water) instead of CaCO(3) buffer. RESULTS: There was no statistical difference detected between RIX4414 vaccine reconstituted with buffer or water in vaccine take or in seroconversion rate. The anti-rotavirus Immunoglobulin A (IgA) seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1-90.0) for the group with buffer and 78.6% (95% CI: 71.2-84.8) for the group with water. Solicited and unsolicited symptoms reported were similar across groups. No vaccine related serious adverse events (SAEs) were reported. METHODS: Healthy infants aged 6-12 weeks, received two oral doses of the RIX4414 vaccine/placebo, reconstituted either with injectable water or CaCO(3) buffer according to a 0, 2 month schedule. Seroconversion rates in terms of anti-RV IgA antibody levels (cut off: >/=20 U/ml by ELISA) and vaccine take were calculated 2 months post-Dose 2. Solicited and unsolicited symptoms reported during the 15- and 31-day follow-up period after each dose and SAE s reported during the entire study period were recorded. CONCLUSION: Administration of RIX4414 vaccine in the absence of CaCO(3) buffer was shown to be well tolerated and immunogenic in Thai infants.

13.
Vaccine ; 27(52): 7428-35, 2009 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-19683087

RESUMO

The immunogenicity and lot-to-lot consistency of an AS03-adjuvanted H5N1 vaccine were evaluated in 1206 Asian adults, randomised to receive two doses of adjuvanted (3.75 microg haemagglutinin) or diluent-mixed vaccines, 21 days apart. Post-Dose 2, 96.0% of vaccinees in the H5N1-AS03 group demonstrated a four-fold increase in neutralising antibody titres against the vaccine strain A/Vietnam/1194/2004 and 91.4% against strain A/Indonesia/05/2005. Haemagglutination-inhibiting antibodies (titre > or = 1:40) against A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains were observed in 94.3% and 50.2% of subjects, respectively. Lot-to-lot consistency of the AS03-adjuvanted vaccine combinations was demonstrated. The AS03-adjuvanted vaccine was well tolerated, induced a high frequency of immune responses to the vaccine strain, allowed antigen sparing and promoted cross-clade immunity. These characteristics make it suitable for presumptive use if an H5N1 pandemic were considered to be imminent.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Anticorpos Antivirais/sangue , Reações Cruzadas/imunologia , Feminino , Testes de Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Imunização Secundária , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Adulto Jovem
14.
J Infect Dis ; 200(1): 33-8, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19473096

RESUMO

BACKGROUND: Transmission of hepatitis B virus (HBV) from carrier mothers to their babies appears to be one of the most important factors influencing the prevalence of chronic HBV infection in areas of high hepatitis B endemicity. METHODS: Infants born to HBV surface antigen (HBsAg)-positive mothers who were or were not positive for HBV e antigen (HBeAg) or to mothers who were negative for both HBsAg and HBeAg have been followed for 17 years for serological evidence of HBV infection. These infants were divided into 2 groups on the basis of their hepatitis B vaccination protocols: group 1 received vaccine at birth and 1, 2, and 12 months later, and group 2 received vaccine at birth and 1 and 6 months later. Follow-up involved annual clinic visits, during which a blood sample was taken and analyzed for the presence of HBsAg, antibody to HBsAg, and antibody to HBV core antigen (HBcAg). Selected blood samples that tested positive for HBV markers during 2 consecutive visits separated by a long interval were further investigated by polymerase chain reaction to detect HBV DNA. RESULTS: Transient presence of HBsAg or transient and/or long-term presence of antibody to HBcAg suggested that this population was heavily exposed to HBV during the follow-up period. Despite these findings, no new cases of chronic HBV infection were observed. None of the subjects with transient presence of HBsAg had any clinical symptoms of liver disease. CONCLUSIONS: This study demonstrates the efficacy of the HBV vaccine and its ability to protect against symptomatic disease.


Assuntos
Antígenos de Superfície da Hepatite B/análise , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B/imunologia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Criança , Feminino , Vacinas contra Hepatite B/uso terapêutico , Antígenos E da Hepatite B/sangue , Humanos , Imunização Secundária , Gravidez , Tailândia
15.
Viral Immunol ; 22(2): 125-30, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19326999

RESUMO

Eighty-seven high-risk individuals in Thailand who had received a complete course of recombinant HBV vaccine 18-20 y ago were investigated with regard to their immunological memory. To evaluate humoral immunity, anti-HBs antibody titers were measured. Cellular immunity was determined by ELISPOT to detect HBV-specific IFN-gamma-producing cells. Overall 83.9% of participants developed circulating anti-HBs (titer > or = 1 mIU/mL) and 58.6% were seroprotected (titer > or = 10 mIU/mL). As for cellular immunity, 50.6% were positive on ELISPOT. Moreover, there was no correlation between the level of anti-HBs and positive ELISPOT results. However, the majority of participants (81.8%) who were positive for IFN-gamma-producing cells were seropositive, but only 50% of seropositive participants were ELISPOT-positive. Thus, 18-20 y after immunization, it appears that a second booster dose should be considered, especially in high-risk groups.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Linfócitos T/imunologia , Adolescente , Hepatite B/prevenção & controle , Humanos , Imunoensaio , Memória Imunológica , Interferon gama/metabolismo , Tailândia , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-19323033

RESUMO

This retrospective study compared the liver function test results and outcomes between children with acute liver failure (ALF) due to dengue hemorrhagic fever (DHF) and due to other causes. We retrospectively reviewed patients less than 15 years old with a diagnosis of ALF admitted to 13 participating centers from different parts of Thailand for the years 2000 and 2001, and those admitted to King Chulalongkorn Memorial Hospital for the year 1997 to 2004. The diagnosis of ALF was based on prothrombin time (PT) prolongation to greater than 2 times the normal control value and the presence of encephalopathy without pre-existing liver disease. The patients were divided into 2 groups: group I (n=16) had DHF with ALF and group II (n=37) had ALF due to other causes. DHF patients had AST levels significantly higher than ALT levels. The mortality rate in group I (50%) was lower than in group II (72.9%), although the difference was not statistically significant. The non-DHF patients who died had a significantly longer duration of jaundice before the onset of encephalopathy and a significantly higher PT ratio compared to survivors. There were no significant differences in the duration of jaundice before the onset of encephalopathy and liver function between dengue patients who died and those who survived.


Assuntos
Encefalopatia Hepática/etiologia , Falência Hepática Aguda/etiologia , Testes de Função Hepática/métodos , Dengue Grave/complicações , Aspartato Aminotransferases/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Encefalopatia Hepática/fisiopatologia , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/fisiopatologia , Masculino , Tempo de Protrombina , Estudos Retrospectivos , Dengue Grave/mortalidade , Dengue Grave/fisiopatologia , Índice de Gravidade de Doença , Tailândia/epidemiologia , Resultado do Tratamento
17.
Am J Trop Med Hyg ; 78(3): 426-33, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18337339

RESUMO

A live-attenuated tetravalent dengue virus (DENV) vaccine candidate has been well tolerated and immunogenic in healthy, US flavivirus naive adult volunteers. We conducted a pilot, safety, and immunogenicity trial of the vaccine candidate in healthy Thai children (6-7 years of age) to prepare for its eventual evaluation in Thai infants. In an uncontrolled, open clinical trial, the investigational vaccine was administered on study Days 0 and 180 to seven volunteers residing in Bangkok without neutralizing antibodies to DENV1-4 or to Japanese encephalitis virus (JEV). Clinical and laboratory safety assessments were completed during the 30 days after each vaccine dose, and immunogenicity was determined at Day 30. In this study, the vaccine was well tolerated with no serious adverse events or alert laboratory values. One volunteer experienced fever (38.2 degrees C, < 2 days) and associated DENV4 vaccine viremia 7 days after Dose 2. One month after Dose 2, six volunteers in the per-protocol analysis exhibited a tetravalent neutralizing antibody response with DENV1-4 geometric mean titers of 55, 475, 350, and 171, respectively. Ten weeks (~75 days) after Dose 2, five of the six volunteers continued to exhibit a tetravalent neutralizing antibody profile; one volunteer's DENV4 PRNT50 titer fell below the assay cut-off (29 --> < 10); (clinicaltrials.gov NCT00384670).


Assuntos
Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/imunologia , Vírus da Dengue , Dengue/imunologia , Criança , Vacinas contra Dengue/administração & dosagem , Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Esquema de Medicação , Feminino , Febre , Humanos , Masculino , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Viremia
18.
Vaccine ; 26(12): 1535-40, 2008 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-18289746

RESUMO

This paper presents 7- and 10-year follow-up immunogenicity data from two studies, which explored long-term persistence induced by combined tetravalent DTPw-HBV vaccines. The 10-year follow-up study compared two identical antigen-content, but different formulations of DTPw-HBV vaccine (adsorbed on either Al(OH)(3) or Al(PO(4)), whilst the 7-year follow-up study compared two different formulations of DTPw-HBV vaccines containing 5 and 10 microg of hepatitis B surface antigen (HBsAg), following a birth dose of HBV. Primary vaccination took place at 2, 4, 6 months and booster dosing at 18 months. A booster dose of local DTPw vaccine was given at 4 years of age to all returning subjects. At the end of the 7-year study, 90.9% subjects receiving 10 microg HBsAg had anti-HBs antibody concentrations > or =10mIU/ml; the majority of subjects remained seroprotected against diphtheria and tetanus (> or =90.9 and 100%, respectively) and 100% had seropositive levels for pertussis antigens. At the end of the 10-year follow-up study, > or =60.9% subjects had seroprotective concentrations of anti-HBs antibodies; > or =95.2 and 100% subjects were seroprotected against diphtheria and tetanus, respectively; > or =78.3% subjects were seropositive for pertussis. The results demonstrate long-term antibody persistence induced by combined DTPw-HBV vaccine.


Assuntos
Envelhecimento/imunologia , Anticorpos Antibacterianos/análise , Anticorpos Antivirais/análise , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas contra Hepatite B/imunologia , Criança , Estudos de Coortes , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Feminino , Vacinas contra Hepatite B/efeitos adversos , Humanos , Imunização Secundária , Lactente , Masculino , Fatores de Tempo , Vacinas Combinadas
19.
Int J Infect Dis ; 12(1): 88-97, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17716936

RESUMO

OBJECTIVE: Safety and reactogenicity of a new heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine was compared with a widely used pentavalent DTPw-HBV/Hib vaccine. METHODS: Three phase III randomized studies comparable in design and methodology, in which healthy infants received DTPw-HBV/Hib-MenAC (N=1334) or DTPw-HBV/Hib (N=446) at 2, 4, and 6 months, were pooled for analysis. Solicited symptoms were recorded for 4 days, and unsolicited adverse events for 31 days after each dose. Serious adverse events (SAEs) were recorded throughout the studies. RESULTS: There were no significant differences between the two groups in the proportion of subjects with fever >39.5 degrees C or >40.0 degrees C (p<0.005). Compared to group DTPw-HBV/Hib, a significantly higher percentage of subjects in group DTPw-HBV/Hib-MenAC reported fever >39 degrees C (21.2% vs. 14.8%, p=0.004). Fever subsided quickly, did not lead to differences in attendance to medical services and did not increase from dose to dose. Sixty-seven SAEs were reported, 56/1334 (4.2%) in group DTPw-HBV/Hib-MenAC and 11/446 (2.5%) in the DTPw-HBV/Hib group. CONCLUSION: Overall, the heptavalent and pentavalent vaccines had similar safety profiles. The difference observed in percentage of subjects with fever >39 degrees C did not lead to differences in medically attended visits for fever.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Febre , Vacinas contra Hepatite B/administração & dosagem , Vacinas Meningocócicas/administração & dosagem , Vacinas Combinadas/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Feminino , Febre/etiologia , Febre/imunologia , Vacinas contra Hepatite B/efeitos adversos , Humanos , Esquemas de Imunização , Imunização Secundária , Lactente , Masculino , Vacinas Meningocócicas/efeitos adversos , Filipinas , Convulsões Febris/etiologia , Convulsões Febris/imunologia , Tailândia , Vacinas Combinadas/efeitos adversos
20.
J Med Assoc Thai ; 90(7): 1330-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17710973

RESUMO

OBJECTIVE: Comparing the immunogenicity and reactogenicity of three vaccine combinations. These were GlaxoSmithKline Biologicals' (GSK) Haemophilus influenzae type b vaccine (Hib-TT, Hiberix) administered with the local Government Pharmaceutical Organization's (GPO) diphtheria-tetanus-pertussis whole cell (DTPw) vaccine, Hib-TT mixed with GPO's DTPw vaccine, or Hib-IT mixed with GSKs' DTPw vaccine (Tritanrix). MATERIAL AND METHOD: An open, randomized, controlled, single center study of three hundred and sixty infants. They were randomized into three groups to receive either Hib-TT Hiberix mix with GPOs' DTPw vaccine (group 1), Hib-TT mixed with GPO's DTPw vaccine (group 2), or Hib-TT mixed with GSKs' DTPw vaccine (Tritanrix; group 3) at two, four and six months of age. RESULT: One month after the third dose, all subjects had antibodies level against Hib polyribosylribitol phosphate (PRP) > or = 0.15 microg/ml. All 11 subjects except two (in group 2) had anti-PRP levels > or = 1.0 microg/ml. The geometric mean concentrations were similar in all three groups. Over 96% of the subjects in all three groups demonstrated an immunological response to diphtheria, tetanus, and pertussis antigens. There was no diference among the three groups in terms of severe local reaction and fever. CONCLUSION: The present study showed that the combined vaccines produced an effective antibody response with no increase in reactogenicity compared to separately administrated vaccines.


Assuntos
Anticorpos Antibacterianos , Vacina contra Difteria, Tétano e Coqueluche/farmacologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/farmacologia , Haemophilus influenzae tipo b/imunologia , Toxoide Tetânico/farmacologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Interações de Medicamentos , Feminino , Infecções por Haemophilus/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Masculino , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Tailândia , Vacinas Combinadas
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