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1.
J Pediatr Gastroenterol Nutr ; 78(6): 1342-1354, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38644678

RESUMO

BACKGROUND: The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS: In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. FINDINGS: Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. INTERPRETATION: The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.


Assuntos
Antivirais , Carbamatos , Combinação de Medicamentos , Hepatite C Crônica , Compostos Heterocíclicos de 4 ou mais Anéis , Sofosbuvir , Humanos , Sofosbuvir/uso terapêutico , Sofosbuvir/farmacocinética , Sofosbuvir/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Criança , Carbamatos/uso terapêutico , Carbamatos/farmacocinética , Carbamatos/efeitos adversos , Carbamatos/administração & dosagem , Masculino , Pré-Escolar , Feminino , Antivirais/uso terapêutico , Antivirais/farmacocinética , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Adolescente , Hepatite C Crônica/tratamento farmacológico , Resultado do Tratamento , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Resposta Viral Sustentada , Genótipo , Benzimidazóis , Benzopiranos
2.
J Viral Hepat ; 30(1): 29-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208116

RESUMO

Antiviral nucleos(t)ide analogue therapies inhibit HBV replication and suppress the HBV DNA levels in patients with chronic HBV infection. Since HBV RNAs are expressed from cccDNA or HBV integrated sequences, independently of viral genome replication, levels of HBV RNAs in plasma may remain high following treatment with nucleos(t)ide analogue. Thus, HBV RNAs have been proposed to be used as a viral biomarker for treatment outcome and disease progression. Recent investigations of plasma HBV RNAs described the presence of full length as well as subgenomic forms of RNA. To support the usage of plasma HBV RNAs as a viral biomarker, further understanding of HBV RNA composition in clinical samples is needed. Here, sequence of extracellular HBV RNAs was characterized in plasma samples of patients with chronic HBV infection using two independent RNA amplification methods that do not use HBV-specific primers for amplification: total RNA (NuGEN RNAseq) and mRNA (TruSeq RNAseq). Sequencing coverage was obtained across the full length of HBV genome for both methods, confirming the presence of full-length HBV RNA in plasma. The sequence of HBV RNA was nearly identical to plasma HBV DNA sequence in each sample with only 0-14 (median 4) mismatches over 3 kb. Thus, sequence of HBV RNA plasma reflects the intrahepatic viral reservoir and can be used for monitoring of sequence variants such as resistance in clinical trials. Additionally, RNA splice forms, different polyA tails start positions and presence of HBV-human chimeric transcript were identified.


Assuntos
Antivirais , Vírus da Hepatite B , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Biomarcadores , DNA Viral , Vírus da Hepatite B/genética , RNA Viral , Replicação Viral , RNA Subgenômico
3.
Hepatology ; 76(2): 445-455, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35112372

RESUMO

BACKGROUND AND AIMS: Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic HCV infection. In the USA and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults who previously received an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8-week or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype. METHODS: In this Phase 2, multicenter study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients. RESULTS: All patients (n = 21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21 of 21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults. CONCLUSIONS: The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.


Assuntos
Hepatite C Crônica , Hepatite C , Adolescente , Adulto , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Carbamatos , Criança , Ciclopropanos , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Cirrose Hepática/tratamento farmacológico , Prolina/análogos & derivados , Quinoxalinas , Sofosbuvir/efeitos adversos , Sulfonamidas , Resposta Viral Sustentada , Resultado do Tratamento
4.
Hepatology ; 71(2): 422-430, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31220349

RESUMO

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event "abnormal drug taste." The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Criança , Pré-Escolar , Feminino , Fluorenos/efeitos adversos , Humanos , Masculino , Sofosbuvir , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos
5.
Hepatology ; 71(1): 31-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222783

RESUMO

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open-label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty-four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%-100%). The patient who did not achieve SVR12 was a 4-year-old who discontinued treatment after 3 days because of "abnormal drug taste." The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3-year-old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Genótipo , Humanos , Masculino , Resposta Viral Sustentada , Resultado do Tratamento
6.
J Clin Microbiol ; 57(4)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30728196

RESUMO

Voxilaprevir is a direct-acting antiviral agent (DAA) that targets the NS3/4A protease of hepatitis C virus (HCV). High sequence diversity of HCV and inadequate drug exposure during unsuccessful treatment may lead to the accumulation of variants with reduced susceptibility to DAAs, including NS3/4A protease inhibitors such as voxilaprevir. The voxilaprevir susceptibility of clinical and laboratory strains of HCV was assessed. The NS3 protease regions of viruses belonging to 6 genotypes and 29 subtypes from 345 DAA-naive or -experienced (including protease inhibitor) patients and 344 genotype 1 to 6 replicons bearing engineered NS3 resistance-associated substitutions (RASs) were tested in transient-transfection assays. The median voxilaprevir 50% effective concentration against NS3 from protease inhibitor-naive patient samples ranged from 0.38 nM for genotype 1 to 5.8 nM for genotype 3. Voxilaprevir susceptibilities of HCV replicons with NS3 RASs were dependent on subtype background and the type and number of substitutions introduced. The majority of RASs known to confer resistance to other protease inhibitors had little to no impact on voxilaprevir susceptibility, except A156L, T, or V in genotype 1 to 4 which conferred >100-fold reductions but exhibited low replication capacity in most genotypes. These data support the use of voxilaprevir in combination with other DAAs in DAA-naive and DAA-experienced patients infected with any subtype of HCV.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Compostos Macrocíclicos/farmacologia , Inibidores de Proteases/farmacologia , Sulfonamidas/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Substituição de Aminoácidos , Ácidos Aminoisobutíricos , Ciclopropanos , Farmacorresistência Viral/genética , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Quinoxalinas
7.
Hepatology ; 68(6): 2158-2166, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30070726

RESUMO

Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)-infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir-sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg-sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Ribavirina/uso terapêutico , Uridina Monofosfato/análogos & derivados , Antivirais/farmacocinética , Benzimidazóis/farmacocinética , Criança , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Fluorenos/farmacocinética , Humanos , Masculino , Ribavirina/farmacocinética , Sofosbuvir , Resposta Viral Sustentada , Uridina Monofosfato/farmacocinética , Uridina Monofosfato/uso terapêutico
8.
J Infect Dis ; 218(11): 1722-1729, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29982508

RESUMO

Background: Hepatitis C virus (HCV) exhibits great genetic diversity and is classified into 7 genotypes (GTs), with varied geographic prevalence. Until the recent development of pangenotypic direct-acting antiviral regimens, the determination of HCV GT was necessary to inform optimal treatment. Methods: Plasma samples with unresolved GT using standard commercial genotyping methods were subjected to HCV full-genome sequencing, and phylogenetic analysis was performed to assign GT. Results: Four patients, previously classified as GT5 by LiPA or Abbott RealTime polymerase chain reaction assays, were identified as infected with a novel HCV GT. This novel HCV GT, GT8, is genetically distinct from previously identified HCV GT1-7 with >30% nucleotide sequence divergence to the established HCV subtypes. All 4 patients were originally from Punjab, India, but now reside in Canada and are epidemiologically unlinked. Despite presence of baseline resistance-associated substitutions within the GT8 virus of all 4 patients (NS3: V36L, Q80K/R; NS5A: Q30S, Y93S), all patients achieved a sustained virologic response; 2 treated with sofosbuvir/velpatasvir/voxilaprevir for 8 weeks, 1 with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and 1 with sofosbuvir plus daclatasvir for 12 weeks. Conclusions: The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.


Assuntos
Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/virologia , Adulto , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Farmacorresistência Viral/genética , Feminino , Variação Genética/genética , Genoma Viral/genética , Genômica , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Humanos , Índia , Masculino , Filogenia , RNA Viral/sangue , RNA Viral/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sequência de RNA
9.
Artigo em Inglês | MEDLINE | ID: mdl-30038044

RESUMO

Tenofovir alafenamide (TAF) has shown equivalent efficacy and improved safety profiles for patients with chronic hepatitis B (CHB) compared to tenofovir disoproxil fumarate (TDF). However, limited data are available for its resistance profiles. In two clinical trials, 1,298 hepatitis E antigen-positive and -negative patients with CHB were randomized 2:1 and treated with TAF (n = 866) or TDF (n = 432). Baseline nucleos(t)ide analog resistance substitutions in HBV polymerase/reverse transcriptase (Pol/RT) were assessed using INNO-LiPA Multi-DR v2/v3. Resistance surveillance was conducted for patients with viremia (HBV DNA ≥ 69IU/ml) by HBV Pol/RT sequencing at week 96 or at discontinuation. In vitro phenotypic analysis was performed for patients with conserved site substitutions or virologic breakthrough while adherent to the study drug. At baseline, the majority of patients harbored virus with wild-type Pol/RT (89.2%), with 10.8% harboring resistance associated mutations. A similar percentage of patients in the TAF or TDF groups qualified for sequence analysis through week 96 (TAF, 11.1%; TDF, 10.9%). Of these, a small percentage of patients experienced virologic breakthrough (TAF, 2.8%; TDF, 3.2%) that was often associated with drug nonadherence (TAF, 30%; TDF, 50%). Across treatment groups, 132 patients qualified for sequence analysis through week 96, with nearly half having no sequence changes from baseline (43.2%). Most sequence changes occurred at polymorphic positions, and no isolates showed a reduction in susceptibility in vitro After 96 weeks, the proportion of patients achieving virus suppression (HBV DNA < 69 IU/ml) was similar across treatment groups, and no substitutions associated with resistance to TAF or TDF were detected. (These studies have been registered at ClinicalTrials.gov under identifiers NCT01940471 and NCT01940341.).


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Viremia/tratamento farmacológico , Adenina/uso terapêutico , Alanina , Farmacorresistência Viral/genética , Genótipo , Humanos , Mutação/genética
11.
Int J Infect Dis ; 113: 36-42, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34560266

RESUMO

OBJECTIVES: Due to limited hepatitis C virus (HCV) sequence availability from patients in Russia, the relationship between subtypes and baseline resistance-associated substitutions (RAS) to direct antiretroviral treatment outcome is not fully understood. METHODS: Deep sequencing of HCV NS3, NS5A, and NS5B sequences was performed on plasma HCV samples from 412 direct-acting antiviral (DAA)-naïve patients from Russia. Phylogenetic analysis was performed to investigate sequence similarities between HCV strains from Russia, Asia, Europe, and North America. Pretreatment HCV RAS was assessed with a 15% cutoff. RESULTS: HCV genotype GT1b and GT3a sequences in Russia were related to strains in Europe and Asia. The prevalence of GT1a and GT2a was low in Russia. In GT1b, the prevalence of NS5A Y93H was lower in Russia (6%) compared with Asia (15%). The prevalence of NS5B L159F was similar between Russia and Europe (26-39%). GT3a RAS prevalence was similar between Russia and Asia, Europe, and North America. The 2k/1b recombinant strain in Russia was related to strains from Europe. A higher prevalence of the NS5A RAS L31M (10%) was observed in 2k/1b sequences compared to GT1b (1-6%). CONCLUSIONS: The prevalence of RASs and the phylogenetic analysis showed similarities in HCV strains between Russia, Europe, and North America. This information may be useful for HCV regimens in Russia.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Farmacorresistência Viral , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Filogenia , Prevalência , Federação Russa/epidemiologia , Proteínas não Estruturais Virais/genética
12.
Open Forum Infect Dis ; 6(3): ofz076, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30949527

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. METHODS: Full-genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A, and/or NS5B to HCV genotype (GT) 1-8 reference strains. RESULTS: A total of 14 653 patients with GT1-6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However, for 19 patients, novel subtypes were identified with <85% homology compared with previously described subtypes. These novel subtypes had the following genotypes: 9 in GT2, 5 in GT4, 2 in GT6, and 1 each in GT1, GT3, and GT5. Despite the presence of polymorphisms at resistance-associated substitution positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. CONCLUSIONS: Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized.

13.
PLoS One ; 11(4): e0153019, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27070145

RESUMO

Sensitive and precise serology assays are needed to measure the humoral response to antigens of respiratory syncytial virus (RSV) following natural infection or vaccination. We developed and evaluated a collection of electrochemiluminescent (ECL) serology assays using four RSV antigens (F, N, Ga and Gb). To assess the merits of ECL technology, the four ECL serology assays were evaluated using a well-characterized "gold standard" panel of acute and convalescent serum samples from fifty-nine RSV-positive and thirty RSV-negative elderly subjects (≥65 years old). The combined results from the four ECL assays demonstrated good concordance to the "gold standard" diagnosis, reaching 95% diagnostic sensitivity and 100% diagnostic specificity. Additionally, a combination of ECL assays provided higher diagnostic sensitivity than a commercially available diagnostic ELISA or cell-based microneutralization assay. In summary, these data demonstrate the advantages of using ECL-based serology assays and highlight their use as a sensitive diagnostic approach to detect recent RSV infection in an elderly population.


Assuntos
Anticorpos Antivirais/sangue , Medições Luminescentes/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Testes Sorológicos/métodos , Idoso , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/sangue , Antígenos Virais/imunologia , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Imunidade Humoral , Lactente , Testes de Neutralização , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas Virais de Fusão/imunologia
14.
Open Virol J ; 6: 12-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22383906

RESUMO

Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3(rd) position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.

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