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1.
Vaccine ; 30(5): 904-10, 2012 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-22154769

RESUMO

BACKGROUND: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. METHODS: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. RESULTS: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10(6) peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. CONCLUSIONS: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.


Assuntos
Vacina contra Herpes Zoster/efeitos adversos , Vacina contra Herpes Zoster/imunologia , Vacinação/efeitos adversos , Vacinação/métodos , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , ELISPOT , Feminino , Vacina contra Herpes Zoster/administração & dosagem , Herpesvirus Humano 3/imunologia , Humanos , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem
2.
BMC Med Genomics ; 2: 7, 2009 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-19203388

RESUMO

BACKGROUND: Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. METHODS: The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. RESULTS: The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. CONCLUSION: Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders.

3.
Vaccine ; 24(47-48): 6875-85, 2006 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-17050042

RESUMO

A new manufacturing process, known as process upgrade varicella vaccine (PUVV) was developed for a refrigerated formulation of varicella vaccine and for an investigational zoster vaccine. Safety and tolerability of a two-dose regimen of high-titered (approximately 50,000 PFU) PUVV were compared to a lower-titer formulation (approximately 5400 PFU) of VARIVAX; in 1366 healthy subjects > or =13 years old. Only one vaccine-related clinical serious adverse experience (pruritus; no hospitalization) was reported, in the VARIVAX group. Injection-site adverse experiences following any dose were higher in the PUVV group, 70.0%, than in the VARIVAX group, 56.2%, but generally were mild. Immunogenicity were similar in both groups in seronegative subjects. PUVV was generally well tolerated, and elicited an immune response similar to that induced by the marketed formulation of VARIVAX.


Assuntos
Vacina contra Varicela/efeitos adversos , Vacina contra Varicela/imunologia , Varicela/imunologia , Varicela/prevenção & controle , Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Adolescente , Anticorpos Antivirais/análise , Anticorpos Antivirais/biossíntese , Formação de Anticorpos/imunologia , Vacina contra Varicela/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Imunidade Celular/imunologia , Interferon gama/biossíntese , Masculino
4.
J Infect Dis ; 188(9): 1336-44, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14593591

RESUMO

The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.


Assuntos
Herpesvirus Humano 3/imunologia , Vacinas Virais/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/imunologia , Divisão Celular/imunologia , Feminino , Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Humanos , Imunidade Celular/imunologia , Imunização Secundária , Técnicas Imunoenzimáticas , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Células Th1/imunologia , Vacinas Atenuadas/imunologia
5.
J Med Virol ; 70 Suppl 1: S38-41, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12627485

RESUMO

An interferon-gamma ELISPOT assay has been developed for assessment of cellular immune responses to Varicella-Zoster Virus (VZV) in large, multi-center clinical vaccine trials. We show that the assay performed best when testing peripheral blood mononuclear cells (PBMCs) that had been isolated and then frozen on the same day as blood was drawn, and that freezing PBMCs from blood that was stored overnight before processing resulted in dramatically reduced responses. This assay was used to monitor cell-mediated immunity (CMI) in response to a booster immunization with an investigational live, attenuated VZV vaccine in an elderly population that had been vaccinated 8-10 years previously. The booster vaccine elicited a 1.6- to 1.7-fold rise in the VZV-specific cellular immune response as measured by the ELISPOT assay. The increase from pre to post booster vaccination response was more pronounced (approximately 2.2-fold rise) in a subset of subjects who had received two prior immunizations with a live, attenuated vaccine.


Assuntos
Vacina contra Varicela/administração & dosagem , Ensaio de Imunoadsorção Enzimática/métodos , Herpesvirus Humano 3/imunologia , Imunidade Celular , Interferon gama/análise , Idoso , Humanos , Imunização Secundária , Técnicas In Vitro , Interferon gama/biossíntese , Linfócitos T/imunologia
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