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1.
Vaccine ; 36(45): 6883-6891, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30244873

RESUMO

BACKGROUND: Pediatric use of pneumococcal conjugate vaccines (PCV) has been associated with significant decrease in disease burden. However, disease caused by non-vaccine serotypes has increased. Safety and immunogenicity of 15-valent PCV (PCV15) containing serotypes included in 13-valent PCV (PCV13) plus serotypes 22F and 33F were evaluated in infants (NCT01215188). METHODS: Infants received adjuvanted PCV15, nonadjuvanted PCV15, or PCV13 at 2, 4, 6, and 12-15 months of age. Safety was monitored for 14 days after each dose. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured at postdose-3, predose-4, and postdose-4. RESULTS: Safety profiles were comparable across vaccination groups. At postdose-3, both PCV15 formulations were non-inferior to PCV13 for 10 of 13 shared serotypes but failed non-inferiority for 3 serotypes (6A, 6B, and 19A) based on proportion of subjects achieving IgG GMC ≥0.35 µg/mL. Adjuvanted PCV15 and nonadjuvanted PCV15 were non-inferior to PCV13 for 11 and 8 shared serotypes, respectively, based on postdose 3 comparisons of GMC ratios. PCV15 induced higher antibodies to serotypes 3, 22F, and 33F than PCV13. CONCLUSIONS: PCV15 displayed acceptable safety profile and induced IgG and OPA to all 15 vaccine serotypes at levels comparable to PCV13 for 10 of 13 shared serotypes. Study identification: V114-003. CLINICALTRIALS.GOV identifier: NCT01215188.


Assuntos
Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia , Feminino , Humanos , Lactente , Masculino , Vacinas Pneumocócicas/uso terapêutico , Sorogrupo , Vacinas Conjugadas/uso terapêutico
2.
Vaccine ; 36(45): 6875-6882, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-29559167

RESUMO

BACKGROUND: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551). METHODS: 691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination. RESULTS: Safety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23). CONCLUSIONS: PCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines. Study identification: V114-002. CLINICALTRIALS.GOV identifier: NCT01513551. © 2018 Merck & Co., Inc.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Vacinas Conjugadas/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia
3.
Hum Vaccin Immunother ; 12(8): 2135-2141, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27002793

RESUMO

PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 µg/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre-vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates.


Assuntos
Formação de Anticorpos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Resultado do Tratamento
4.
Vaccine ; 33(24): 2793-9, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25913828

RESUMO

BACKGROUND: Pneumococcal disease remains an important health priority despite successful implementation of pneumococcal conjugate vaccines (PCVs) in infant immunization programs, mainly due to the emergence of diseases caused by serotypes not included in licensed PCVs. A 15-valent pneumococcal conjugate vaccine (PCV-15) containing the 7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) included in licensed PCV-7 available at study initiation plus 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in healthy adults 18-45 years of age. METHODS: Sixty subjects received one dose of PCV-15 or PCV-7. Injection-site and systemic adverse events (AEs) were collected for 14-days postvaccination and serious AEs were collected for 30-days postvaccination. Safety laboratory tests (hematology, chemistry, and urinalysis) were evaluated prior to vaccination and 14-days postvaccination. Serotype-specific IgG and opsonophagocytic killing activity (OPA) responses to 15 serotypes included in PCV-15 were measured immediately prior to vaccination and 30-days postvaccination. RESULTS: AE incidences were comparable between vaccine groups although numerically higher frequencies of erythema (33.3% versus 13.3%), swelling (50.0% versus 23.3%), and myalgia (63.3% versus 36.7%) were reported among PCV-15 versus PCV-7 recipients. Majority of AEs, irrespective of vaccine received, were transient and of mild-to-moderate intensity. No clinically significant differences were observed when comparing AE duration and severity. No laboratory abnormalities, vaccine-related SAEs or discontinuations from the study due to AEs were reported. IgG concentrations for the shared serotypes substantially increased postvaccination at comparable levels between recipients of PCV-15 and PCV-7. Substantial increases in antibody (IgG and OPA) responses to 8 serotypes unique to PCV-15 were observed in PCV-15 recipients. Slight increases to 2 serotypes unique to PCV-15, serotypes 6A and 19A, were also noted in PCV-7 recipients. CONCLUSION: PCV-15 displays an acceptable safety profile and induces IgG and OPA responses to all serotypes included in the vaccine.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Método Duplo-Cego , Eritema/etiologia , Feminino , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Vacina Pneumocócica Conjugada Heptavalente/efeitos adversos , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Vacinação , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia , Adulto Jovem
5.
Pediatr Infect Dis J ; 34(2): 186-94, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25741971

RESUMO

BACKGROUND: Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) in children has led to significant reduction in pneumococcal disease in children and adults. However, diseases caused by serotypes not included in PCV7 have increased. A 15-valent pneumococcal conjugate vaccine (PCV15) containing serotypes in PCV7 and 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in toddlers 12 to 15 months of age. METHODS: Ninety toddlers who completed an infant series with PCV7 received a single dose of either aluminum-adjuvanted PCV15, nonadjuvanted PCV15, or PCV7. Injection-site and systemic adverse events (AEs) were collected for 14 days postvaccination and serious AEs (SAEs) were collected for 30 days postvaccination. Solicited AEs included local (pain/tenderness, swelling, nodule and redness) and systemic (fatigue, arthralgia and myalgia) AEs. Serotype-specific immunoglobulin G (IgG) and opsonophagocytic (OPA) responses were measured immediately prior and 30 days postvaccination. RESULTS: Incidences of local and systemic AEs were comparable across vaccine groups. The majority of reported events, regardless of vaccine received, were transient and of mild to moderate intensity. No clinically significant differences were observed when comparing duration and severity of AEs. No vaccine-related SAEs or discontinuations from the study due to AEs were reported. Pneumococcal IgG concentrations and OPA titers increased postvaccination, with appreciable fold rises for all serotypes. Antibody levels were comparable between both PCV15 formulations and generally comparable to PCV7 for the shared serotypes. CONCLUSION: Both formulations of PCV15 display acceptable safety profiles and induce IgG and OPA responses to all vaccine serotypes.


Assuntos
Anticorpos Antibacterianos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Proteínas Opsonizantes/sangue , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Fagocitose , Vacinas Pneumocócicas/administração & dosagem , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
6.
Clin Vaccine Immunol ; 18(10): 1744-51, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21813660

RESUMO

The measurement of serotype-specific anti-capsular polysaccharide antibodies remains the mainstay of pneumococcal (Pn) vaccine evaluation. New methods that allow the simultaneous measurement of antibodies to several antigens in small volumes of serum, and that agree well with existing techniques, are urgently required to support the increasing number of concomitant vaccines delivered in the infant immunization schedules and the use of extended-valency Pn vaccines. We therefore compared a relatively new multiplexed platform for measuring anti-Pn antibodies with the existing WHO consensus enzyme-linked immunosorbent assay (ELISA). A panel of 50 pediatric samples (34 collected after receipt of a heptavalent pneumococcal conjugate vaccine [PCV7] and 16 without PCV7) was analyzed across two different laboratories using a new multiplex electrochemiluminescence (ECL)-based detection assay developed for the quantitation of IgG serotype-specific antipneumococcal antibodies, and the results were compared to those obtained using the WHO consensus ELISA. For the seven serotypes measured, there was good agreement between the techniques and laboratories. The most notable difference was found between the ECL assay and the ELISA: concentrations tended to be higher in the ECL assay. For serotypes 6B, 9V, 18C, and 23F, the average increases in concentration ranged from 48 to 102%. However, the agreement rates on the proportions of samples with concentrations surrounding 0.35 µg/ml were >82% for all serotypes tested. Agreement between the two laboratories running the ECL assay was generally good: agreement on proportions of samples with concentrations surrounding 0.35 µg/ml was in excess of 92%, and agreement on average antibody concentrations was within 31%. We conclude that the Meso Scale Discovery (MSD) platform provides a promising new technique for the simultaneous measurement of antipneumococcal antibodies.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/imunologia , Técnicas de Laboratório Clínico/métodos , Imunoglobulina G/sangue , Vacinas Pneumocócicas/imunologia , Humanos , Imunoensaio/métodos
7.
Hum Vaccin ; 7(9): 919-28, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21860256

RESUMO

In a study of older adults, first and second doses of 23-valent pneumococcal polysaccharide vaccine (PN23) induced IgG increases for all 8 vaccine serotypes tested. Participants (N=143, mean age 76 years) were re-enrolled to study antibody levels after ten years, and safety and immunogenicity of another PN23 dose. Ten years after first or second doses, mean IgG concentrations exceeded vaccine-naïve levels for 7 of 8 serotypes tested. Second and third doses administered at this time were generally well tolerated and were immunogenic, inducing similar postvaccination levels. Immunogenicity is preserved after multiple PN23 doses without evidence of a lower than expected immune response (i.e., without hyporesponsiveness).


Assuntos
Anticorpos Antibacterianos/sangue , Esquemas de Imunização , Imunoglobulina G/sangue , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/prevenção & controle , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Feminino , Seguimentos , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/imunologia , Fatores de Tempo
8.
J Infect Dis ; 201(4): 516-24, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20092407

RESUMO

BACKGROUND: This study assessed antibody levels for 5 years after primary vaccination or revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23). METHODS: Subjects were enrolled into 4 study groups by age (50-64 or > or = 65 years) and prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously). Blood was obtained on day 0 (before primary vaccination or revaccination), day 30, day 60, and annually during years 2-5. Levels of immunoglobulin G (IgG) to 8 vaccine serotypes were measured by enzyme-linked immunosorbent assay. RESULTS: Of 1008 enrolled subjects, 551 completed year 5. For each serotype and age group, baseline geometric mean concentrations (GMCs) of IgG were higher in revaccination than primary vaccination subjects. Primary vaccination or revaccination with PN23 induced significant increases in levels of antibody to all serotypes tested. Although day 30 and 60 antibody levels tended to be modestly lower after revaccination, study groups had similar GMCs at later time points. For serotypes 4, 6B, 8, 9V, 12F, 14, and 23F, GMCs during years 2-5 after primary vaccination or revaccination remained higher than in vaccine-naive persons. Levels of antibody to serotype 3 returned to baseline by year 2. CONCLUSIONS: Both primary vaccination and revaccination with PN23 induce antibody responses that persist during 5 years of observation.


Assuntos
Anticorpos Antibacterianos/sangue , Imunização Secundária , Imunoglobulina G/sangue , Vacinas Pneumocócicas/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Esquemas de Imunização , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Placebos , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos
9.
J Infect Dis ; 201(4): 525-33, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20088694

RESUMO

BACKGROUND: Older adults are at high risk of developing invasive pneumococcal disease, but the optimal timing and number of vaccine doses needed to prevent disease among this group are unknown. We compared revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23) with primary vaccination for eliciting initial and persistent functional antibody responses. METHODS: Subjects aged > or = 65 years were enrolled. Functional (opsonic) and total immunoglobulin (Ig) G antibody levels were measured following either PN23 primary vaccination (n = 60) or revaccination 3-5 years after receiving a first PN23 vaccination (n = 60). Antibody against vaccine serotypes 4, 14, and 23F was measured at prevaccination (day 0), 30 days after vaccination, and 5 years after vaccination. RESULTS: By day 30, both primary vaccination and revaccination induced significant increases in opsonic and IgG antibody levels. Day 30 levels following revaccination were slightly lower but not significantly different than those after primary vaccination. Year 5 levels were similar in both groups and remained significantly higher than prevaccination levels for primary vaccination subjects. There was good agreement between postvaccination opsonic and IgG antibody levels. CONCLUSIONS: Revaccination of older adults with PN23 was comparable to primary vaccination for inducing elevated and persistent functional and IgG antibody responses.


Assuntos
Anticorpos Antibacterianos/imunologia , Imunização Secundária , Imunoglobulina G/imunologia , Vacinas Pneumocócicas/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/metabolismo , Modelos Lineares , Estudos Longitudinais , Masculino , Vacinas Pneumocócicas/administração & dosagem
10.
J Infect Dis ; 200(7): 1068-77, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19712037

RESUMO

BACKGROUND: The objectives of this study were to evaluate the association between varicella-zoster virus (VZV)-specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine. METHODS: In 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-gamma enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). RESULTS: Robust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower. CONCLUSIONS: Higher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI.


Assuntos
Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/imunologia , Vacinas Virais/imunologia , Idoso , Anticorpos Antivirais/sangue , Método Duplo-Cego , Feminino , Herpes Zoster/imunologia , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/prevenção & controle , Fatores de Tempo
11.
Pediatr Transplant ; 13(8): 1007-13, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19207222

RESUMO

Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first two yr following transplantation. Eligible subjects given a two-dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, six wk post-OMVV, pretransplantation and up to 24 months post-transplantation. Seroprotection was defined as >or=5 gpEU. Twenty-one seronegative children were vaccinated. Following 42 doses, no vaccine-related serious AE occurred. Mab_titer were 17.8 (5.7-910.2) and 183.5 EU (18.8-8116.4) at six and 12 wk, respectively (p < 0.0001). Fourteen (66.7%) participants were transplanted at a median of 16 months (1.5-56) following OMVV and had Mab_titer of 27.2 EU (9.0-236.2) just prior to transplantation. Of 11 who had post-transplantation serology, seroprotection was sustained at three, six and 12 months post-transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two-yr follow-up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to two yr post-transplantation and was not associated with any serious adverse consequences.


Assuntos
Vacina contra Varicela/imunologia , Varicela/prevenção & controle , Imunidade Humoral , Transplante de Órgãos , Imunologia de Transplantes , Adolescente , Varicela/imunologia , Vacina contra Varicela/administração & dosagem , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Terapia de Imunossupressão/métodos , Lactente , Contagem de Linfócitos , Masculino , Estatísticas não Paramétricas
12.
Clin Vaccine Immunol ; 16(3): 387-96, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19158284

RESUMO

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 microg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation (r value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Medições Luminescentes/métodos , Soro/imunologia , Streptococcus pneumoniae/imunologia , Reações Cruzadas , Humanos , Imunoensaio/métodos , Sensibilidade e Especificidade
13.
J Immunoassay Immunochem ; 29(4): 332-47, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18821408

RESUMO

Immunogenicity is often a critical clinical endpoint in the assessment of vaccines prior to the submission of data to regulatory agencies. As a result, the assays used to measure immunogenicity must be highly characterized, well-controlled, and statistically supported. These goals are not easily attained, however, when the development of the assay must occur prior to the first-in-man studies. Two significant barriers exist in the development of these assays: (1) the lack of experience with the performance of a novel antigen in a clinical assay, and (2) the lack of available proper human clinical samples to create reference standards and assess sample matrices. To help to overcome these obstacles, we employed a screening experimental design to assess assay optimization. Design of experiments (DOE) is a statistical tool that allows for the evaluation of all of the key assay parameters to determine the optimal conditions for the assay, as well as determine if there are any interactions of these parameters on the response of the assay. The multivariate approach that is integral to DOE helps to overcome the lack of experience with the assay reagents by facilitating an understanding of how the variables work together in the performance of the assay. Here, we outline the use of full and fractional factorial DOE in the optimization of a clinical assay on two platforms, Luminex and ELISA, for the measurement of antibodies to the beta-amyloid peptide (Abeta) for a novel first-in-man vaccine program. Both platforms are evaluated in an attempt to determine the assay best suited to the needs of the program. We also describe the specificity experiments performed to further characterize the utility of each assay platform.


Assuntos
Vacinas contra Alzheimer/imunologia , Peptídeos beta-Amiloides/imunologia , Ensaio de Imunoadsorção Enzimática/normas , Imunoglobulina G/sangue , Fragmentos de Peptídeos/imunologia , Projetos de Pesquisa/normas , Vacinas contra Alzheimer/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Humanos
14.
J Med Virol ; 78(12): 1679-87, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17063506

RESUMO

Varicella is a highly contagious viral disease found throughout the world. A live-attenuated Varicella-Zoster virus (VZV) vaccine (Oka/Merck strain), VARIVAXtrade mark, was licensed in the United States (US) in 1995 and was made a part of the US recommended childhood vaccination schedule in 1996. The immune response to VZV-containing vaccines has been measured using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to glycoproteins from VZV. A correlate for protective immunity has been established between anti-VZV glycoprotein antibody levels and protection against breakthrough varicella in children, and this correlate is used as the primary immunogenicity endpoint in clinical trials with VZV-containing vaccines. The performance of the "first generation" validated version of the assay was recently reevaluated in order to identify areas for improvement. Specific format and reagent changes were implemented, with the goal of improving assay consistency by maintaining tighter control over assay processes and reagents. An extensive validation of the "second generation" gpELISA was undertaken in order to characterize the updated assay. In this article, we describe the gpELISA method, detail the procedures used to evaluate assay performance, and present the operating characteristics of the second generation gpELISA.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Varicela/imunologia , Glicoproteínas/imunologia , Herpesvirus Humano 3/imunologia , Kit de Reagentes para Diagnóstico , Proteínas do Envelope Viral/imunologia , Adulto , Varicela/imunologia , Varicela/prevenção & controle , Vacina contra Varicela/administração & dosagem , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Humanos , Lactente , Sensibilidade e Especificidade
15.
Clin Vaccine Immunol ; 13(8): 905-12, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16893991

RESUMO

The Merck pneumococcal (Pn) enzyme-linked immunosorbent assays (ELISAs) for measuring antibodies to 12 serotypes (serotypes 1, 3, 4, 6B, 7F, 8, 9V, 12F, 14, 18C, 19F, and 23F) were validated in 1999. Merck Laboratories developed the Pn assays using 10 microg/ml C polysaccharide, 100 microg/ml Pn polysaccharide (PnPs) 25, and 100 microg/ml PnPs 72 for preadsorption of samples, standards, and controls in order to improve the specificity to the Pn serotypes in the vaccine. The Pn assays utilize postimmunization sera obtained from subjects immunized with PNEUMOVAX 23 as standards for measuring immunoglobulin G concentrations in sera obtained from vaccine clinical trials with adults and infants. This material was calibrated to the Pn reference standard serum, 89SF, subjected to the Merck Pn ELISA adsorbants. Comparisons were made between the Merck Pn assay and the international Pn assay, showing moderate agreement between the two assay formats. This work describes the test procedures and operating characteristics of the Merck Pn assays and the results of experiments performed to compare the Merck Pn ELISAs to the international Pn ELISAs.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Pneumocócicas/normas , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Vacinas/normas , Organização Mundial da Saúde , Adulto , Calibragem , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Lactente , Vacinas Pneumocócicas/imunologia , Padrões de Referência , Sensibilidade e Especificidade , Sorotipagem , Vacinas/imunologia
16.
Vaccine ; 21(5-6): 419-30, 2003 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-12531640

RESUMO

T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to naïve T cells. These naïve T cells are stimulated to proliferate and differentiate into effector and memory T cells. Activated, effector and memory T cells provide B cell help in the lymph nodes and traffic to sites of infection where they secrete anti-microbial cytokines and kill infected cells. At least two types of memory cells have been defined in humans based on their functional and migratory properties. T central-memory (T(CM)) cells are found predominantly in lymphoid organs and can not be immediately activated, whereas T effector-memory (T(EM)) cells are found predominantly in peripheral tissue and sites of inflammation and exhibit rapid effector function. Most currently licensed vaccines induce antibody responses capable of mediating long-term protection against lytic viruses such as influenza and small pox. In contrast, vaccines against chronic pathogens that require cell-mediated immune responses to control, such as malaria, Mycobacterium tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis C virus (HCV), are currently not available or are ineffective. Understanding the mechanisms by which long-lived cellular immune responses are generated following vaccination should facilitate the development of safe and effective vaccines against these emerging diseases. Here, we review the current literature with respect to memory T cells and their implications to vaccine development.


Assuntos
Memória Imunológica/imunologia , Linfócitos T/imunologia , Vacinas/imunologia , Animais , Humanos , Imunidade Celular/imunologia
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