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1.
Hum Vaccin Immunother ; : 1-8, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31216205

RESUMEN

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ). Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment. At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant. As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.

2.
J Infect Dis ; 217(11): 1750-1760, 2018 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-29529222

RESUMEN

Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration: NCT01165177; NCT01165229.

3.
Hum Vaccin Immunother ; 14(6): 1370-1377, 2018 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-29461919

RESUMEN

BACKGROUND: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination. METHODS: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination. RESULTS: Participants' mean age at dose 1 was 72.3 years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, ≥70 years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15. CONCLUSION: In adults aged ≥60 years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination. SUMMARY: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15 years post initial vaccination.

4.
Leuk Lymphoma ; 59(5): 1172-1179, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28831836

RESUMEN

We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.

6.
Vaccine ; 35(6): 909-915, 2017 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-28069358

RESUMEN

OBJECTIVES: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune-suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). METHODS: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated ⩾3weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. RESULTS: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p<0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. CONCLUSION: Patients vaccinated with PPSV within 10days after neurotrauma or neurosurgery respond similarly to those vaccinated after ⩾3weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery. CLINICAL TRIALS REGISTRATION: NCT02806284.


Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Hipófisis/inmunología , Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/prevención & control , Fractura Craneal Basilar/inmunología , Vacunación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Esquemas de Inmunización , Inmunoglobulina G/biosíntesis , Masculino , Persona de Mediana Edad , Hipófisis/patología , Hipófisis/cirugía , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/microbiología , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/inmunología , Serogrupo , Fractura Craneal Basilar/patología , Fractura Craneal Basilar/cirugía , Hueso Esfenoides/inmunología , Hueso Esfenoides/cirugía , Streptococcus pneumoniae/inmunología , Factores de Tiempo
7.
Infect Dis (Lond) ; 48(6): 443-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27030917

RESUMEN

BACKGROUND: Due to an outbreak of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. METHODS: A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. RESULTS: Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. CONCLUSIONS: Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/prevención & control , Ciprofloxacino/uso terapéutico , Leucemia/tratamiento farmacológico , Leucemia/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/sangre , Bacteriemia/microbiología , Bacteriemia/prevención & control , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Carbapenémicos/uso terapéutico , Estudios de Cohortes , Neutropenia Febril/microbiología , Neutropenia Febril/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Micosis/prevención & control
8.
Vaccine ; 34(5): 650-655, 2016 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-26718689

RESUMEN

BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX). METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥ 60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test. RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05). CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.


Asunto(s)
Artritis Reumatoide/inmunología , Encefalitis Transmitida por Garrapatas/prevención & control , Huésped Inmunocomprometido , Vacunas Virales/uso terapéutico , Adulto , Anciano , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Inmunización Secundaria , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Vacunas Virales/inmunología
9.
Vaccine ; 34(6): 863-8, 2016 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-26432913

RESUMEN

BACKGROUND: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01B adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25µg, 50µg, or 100µg gE) was conducted in adults ≥60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50µg gE/AS01B formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination. METHODS: This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing ≥2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose. RESULTS: Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72. CONCLUSIONS: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.


Asunto(s)
Vacuna contra el Herpes Zóster/uso terapéutico , Herpes Zóster/prevención & control , Inmunidad Celular , Inmunidad Humoral , Vacunas de Subunidad/uso terapéutico , Proteínas del Envoltorio Viral/inmunología , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Linfocitos T CD4-Positivos/inmunología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Vacuna contra el Herpes Zóster/inmunología , Humanos , Lípido A/administración & dosificación , Lípido A/análogos & derivados , Masculino , Persona de Mediana Edad , Saponinas/administración & dosificación , Vacunas de Subunidad/inmunología
10.
J Infect ; 70(6): 577-84, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25562448

RESUMEN

BACKGROUND: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. METHODS: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. RESULTS: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log10 anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 ± 0.15, 1.38 ± 0.15 and 1.81 ± 0.12 µg/ml, respectively. CONCLUSIONS: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae tipo b/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/inmunología , Femenino , Vacunas contra Haemophilus/inmunología , Humanos , Masculino , Persona de Mediana Edad , Neurocirugia , Linfocitos T/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Adulto Joven
11.
Transplantation ; 99(5): 1036-42, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25211518

RESUMEN

BACKGROUND: The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics. METHODS: Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records. RESULTS: Based on a cutoff level of 29 FoxP3 cells per mm, most (80%) of the PTLDs were FoxP3. Forty-seven of 74 PTLDs displayed no FoxP3 cells at all. The frequency of FoxP3 cells did not influence median overall survival. The FoxP3 PTLDs were more frequently of T-cell phenotype (P = 0.04), located at the graft (P = 0.03), occurred earlier after transplantation (P = 0.04), were more likely to develop in lung recipients (P = 0.04), and in patients that had received anti-T-cell globulin as induction therapy (P = 0.02). The FoxP3 PTLDs were associated with hepatitis C seropositivity (P = 0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity. CONCLUSION: Our findings suggest that intratumoral FoxP3 Tregs do not influence survival in patients with PTLD. FoxP3 Tregs are rare in PTLD, possibly because of heavy immunosuppression.


Asunto(s)
Factores de Transcripción Forkhead/análisis , Trastornos Linfoproliferativos/inmunología , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Inmunosupresores/uso terapéutico , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/mortalidad
12.
Acta Oncol ; 53(9): 1212-20, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24865118

RESUMEN

UNLABELLED: It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. MATERIAL AND METHODS: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP(®). RESULTS: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI ≥ 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. CONCLUSION: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Neoplasias/inmunología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Anticuerpos/sangre , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunoglobulina G/sangre , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Estudios Prospectivos , Rituximab , Suecia , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Adulto Joven
13.
Clin Vaccine Immunol ; 21(5): 651-60, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24599529

RESUMEN

Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 µg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02V than with alum, higher with a dose of 30 µg than with 10 µg for PhtD-dPly and higher with 30-µg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-µg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.).


Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Compuestos de Alumbre/efectos adversos , Antígenos Bacterianos/inmunología , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Saponinas/efectos adversos , Estreptolisinas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Anciano , Anciano de 80 o más Años , Compuestos de Alumbre/administración & dosificación , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Proteínas Opsoninas/sangre , Fagocitosis , Placebos/administración & dosificación , Vacunas Neumococicas/administración & dosificación , Saponinas/administración & dosificación , Método Simple Ciego , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunología
14.
Vaccine ; 32(15): 1745-53, 2014 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-24508036

RESUMEN

BACKGROUND: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system AS01B. METHODS: In this phase II, single-blind, randomized, controlled study, adults aged ≥60years (N=714) received one dose of 100µggE/AS01B, two doses, two months apart, of 25, 50, or 100µggE/AS01B, or two doses of unadjuvanted 100µggE/saline. Frequencies of CD4(+) T cells expressing ≥2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. RESULTS: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01B formulations than after one dose of 100µggE/AS01B or two doses of 100µggE/saline. Frequencies were comparable after two doses of 25, 50, or 100µggE/AS01B. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100µggE/AS01B and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline. CONCLUSIONS: The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged ≥60years. Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).


Asunto(s)
Vacuna contra el Herpes Zóster/inmunología , Inmunidad Celular , Inmunidad Humoral , Adyuvantes Inmunológicos/administración & dosificación , Anciano , Anticuerpos Antivirales/sangre , Linfocitos T CD4-Positivos/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/uso terapéutico , Humanos , Esquemas de Inmunización , Masculino , Persona de Mediana Edad , Método Simple Ciego , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/uso terapéutico
15.
Acta Oncol ; 53(5): 669-79, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24164103

RESUMEN

BACKGROUND: Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant. MATERIALS AND METHODS: We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980-2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records. RESULTS: Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection. CONCLUSIONS: With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.


Asunto(s)
Linfoma/epidemiología , Linfoma/etiología , Trasplante de Órganos/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Hepatitis C/complicaciones , Humanos , Incidencia , Lactante , Linfoma/patología , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Adulto Joven
16.
Artículo en Inglés | MEDLINE | ID: mdl-24003363

RESUMEN

INTRODUCTION: In Sweden in 2009, two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine were recommended for those with HIV infection along with one dose of seasonal trivalent influenza vaccine (TIV). At that time, no data for HIV patients and their response to the adjuvanted vaccine were available. METHODS: Forty-two HIV-infected individuals were vaccinated with the pandemic vaccine on study days 0 and 28. Twenty-one of them received TIV on day 56 and 21 did not. Serum samples were taken at these time points, and also on day 86 and after 1 year for serologic analyses. RESULTS: Before vaccination, none of the 42 patients had putatively protective levels of antibodies (haemagglutination inhibition [HI] titres ≥1:40) to the pandemic-like strain A/California/7/2009 H1N1. After dose 1, the seroprotection rate (SPR) and seroconversion rate (SCR) were both 69% (29 of 42). After dose 2, the SPR and SCR were 89 and 86%, respectively. At 1 year, 10 (34%) of 29 had protective antibodies and 16 (62%) of 26 who had had protective antibody levels had lost them. There was a retained factor increase of the geometric mean titre (GMT) of 3.9. Serological analyses could be performed in 19 subjects who were vaccinated with TIV and in 21 who were not. Protective antibodies to the three strains before vaccination were 20-37%. The SCR was 26% to A/Brisbane/59/2007 H1N1, 47% to A/Uruguay/10/2007/ H3N2 and 42% to B/Brisbane/60/2008. At 1 year, the factor increase of GMT was 1.8 to the two influenza A strains. CONCLUSION: Two doses of adjuvanted influenza vaccine improved the SCR and the SPR among HIV-infected subjects. Long-term follow-up indicates revaccination in the next influenza season whether they received an adjuvanted or non-adjuvanted influenza vaccine.

17.
BMC Infect Dis ; 13: 348, 2013 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-23890405

RESUMEN

BACKGROUND: Improved influenza vaccines are needed to reduce influenza-associated complications in older adults. The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people. METHODS: This observer-blind, randomized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged ≥65 years. Participants were randomized (~200 per group) to receive one dose of non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System (AS03(C), AS03(B) or AS03(A), with 2.97, 5.93 and 11.86 mg tocopherol, respectively) together with the immunostimulant monophosphoryl lipid A (MPL, doses of 0, 25 or 50 mg). Hemagglutination-inhibition (HI) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination. The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90% confidence interval was transformed into a desirability index (a value between 0 and 1) in an experimental domain for each vaccine strain, and plotted in relation to the AS03 and MPL dose combination in the formulation. This model was used to assess the optimal formulation based on HI antibody titers. Reactogenicity and safety were also assessed. The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine. RESULTS: In the HI antibody-based model, an AS03 dose-response was evident; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine, and for the AS03(A)-MPL25, AS03(B)-MPL25 and AS03(B)-MPL50 formulations against the B strain. Modelling using more stringent criteria (post hoc) showed a clear dose-range effect for the AS03 component against all strains, whereas MPL showed a limited effect. Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations (AS03(C) and AS03(B)-MPL25). Reactogenicity increased with increasing AS03 dosage, and with MPL. No safety concerns were raised. CONCLUSIONS: Five formulations containing AS03(A) or AS03(B) were identified as potential candidates to improve immune responses to influenza vaccination; AS03(B) without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT00540592.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Adyuvantes Inmunológicos/efectos adversos , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Femenino , Humanos , Vacunas contra la Influenza/efectos adversos , Masculino , Persona de Mediana Edad , Modelos Inmunológicos
18.
Vaccine ; 31(35): 3585-93, 2013 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-23688527

RESUMEN

BACKGROUND: The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13). METHODS: We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination. RESULTS: Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment. CONCLUSION: In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13.


Asunto(s)
Inmunización Secundaria , Vacunas Neumococicas , Neumonía Neumocócica/prevención & control , Streptococcus pneumoniae/inmunología , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/inmunología , Polisacáridos Bacterianos/inmunología , Estados Unidos , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/uso terapéutico
19.
Eur J Haematol ; 90(5): 413-9, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23444982

RESUMEN

BACKGROUND: Patients with hematological malignancies are more susceptible to viral infections including influenza. In 2009, the World Health Organization classified the novel influenza A (H1N1) virus as pandemic. The potential impact of this pandemic for patients with hematological disorders was unknown. Institutional guidelines recommended two doses of AS03-adjuvanted influenza A (H1N1) 2009 pandemic vaccine for these patients. OBJECTIVES: We aimed to determine the safety, immunogenicity, and clinical efficacy of this vaccine in patients with hematological diseases. Furthermore, we compared the immunological responses to that obtained by the non-adjuvanted trivalent seasonal influenza vaccine (TIV). METHODS: All included patients received adjuvanted pandemic vaccine and the majority received TIV. Serum for antibody analyses was collected at five time points. RESULTS: Thirty-one patients with different hematological diseases were included. After the second vaccine dose, a total of 25 (81%) reached both protective levels of antibodies and seroconversion response. Antibody titers ≥ 1 : 40 persisted for 50% of responding patients at 1 yr. Seroconversion was observed in 69% of 14 patients who had undergone hematopoietic stem cell transplantation and in all (9/9) patients with myeloma (five with ongoing treatment including high-dose corticosteroids). After vaccination with TIV, seroconversions against the three included strains were detected in 28%, 40%, and 20%. Response to the adjuvanted pandemic vaccine was superior (P < 0.009). CONCLUSIONS: A substantial proportion of patients with hematological malignancies including patients undergoing chemotherapy mounted a good response to the adjuvanted pandemic vaccine. This vaccine had superior immunogenicity as compared to the non-adjuvanted TIV.


Asunto(s)
Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/complicaciones , Gripe Humana/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Pruebas de Inhibición de Hemaglutinación , Enfermedades Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Vaccine ; 28(15): 2730-4, 2010 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-20117269

RESUMEN

The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (> or =0.15 microg/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant.


Asunto(s)
Vacunas Neumococicas/inmunología , Trasplante de Células Madre , Trasplante Homólogo , Trasplante , Vacunación/métodos , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Niño , Femenino , Vacuna Neumocócica Conjugada Heptavalente , Humanos , Masculino , Persona de Mediana Edad , Streptococcus pneumoniae/inmunología , Adulto Joven
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