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1.
Vaccine X ; 6: 100074, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33005887

RESUMO

INTRODUCTION: Japanese encephalitis (JE) virus is the leading cause of viral encephalitis across temperate and tropical zones of Asia. The live attenuated SA 14-14-2 JE vaccine (CD-JEV) is one of three vaccines prequalified by the World Health Organization (WHO) to prevent JE. When incorporating a new vaccine into a country's Expanded Program on Immunization (EPI), it is important to show that the new vaccine can be administered concurrently with other routine pediatric vaccines without impairing the immune responses or changing the safety profiles of the co-administered vaccines. This Phase 4 open-label study evaluated the safety and immunogenicity of measles-mumps-rubella (MMR) vaccine co-administered with CD-JEV. METHODS: The study randomized 628 healthy Filipino children aged between 9 and 10 months to receive MMR and CD-JEV concurrently or separately. MMR immunogenicity was measured 56 days after MMR vaccination using a measles plaque reduction neutralization test (PRNT), anti-mumps immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), and anti-rubella IgG ELISA, respectively. Neutralizing antibody against JE virus was measured 28 days after CD-JEV vaccination using PRNT. Safety was assessed through solicitation of immediate reactions, adverse events (AEs) within 14 days of vaccination, unsolicited AEs occurring within 28 days, and serious adverse events (SAEs) during participation in the study. RESULTS/CONCLUSIONS: During the study, no post-vaccinal encephalitis cases or related SAEs were reported in either group. Concurrent immunization with CD-JEV and MMR vaccines was not associated with any unusual safety signals when compared with sequential immunization. No significant differences between the regimens were seen in seropositivity or serology titer/concentration results for any of the antigens. Co-administration of CD-JEV and MMR was non-inferior to single administration of either vaccine.

2.
J Pediatric Infect Dis Soc ; 9(6): 752-755, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31644795

RESUMO

In this study, we illustrate, for the first time, that preexisting low-avidity neutralizing measles maternal antibodies do not interfere with the development of high concentrations of high-avidity measles antibodies in children immunized at age 12 months. This suggests that the quality of measles maternal antibodies, rather than the quantity, impacts immunogenicity of primary measles immunization.


Assuntos
Sarampo , Caxumba , Anticorpos Antivirais , Formação de Anticorpos , Criança , Humanos , Lactente , Sarampo/prevenção & controle , Vacina contra Sarampo , Vacina contra Sarampo-Caxumba-Rubéola
3.
Vaccine ; 38(2): 101-106, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31706809

RESUMO

Respiratory syncytial virus (RSV), is a common cause of serious acute lower respiratory tract illness in infants and young children, causing substantial morbidity and mortality globally. Treatment is mainly supportive and currently there is no licensed preventive vaccine. Clinical trials conducted in the 1960s evaluating a formalin-inactivated RSV vaccine (FI-RSV) in RSV-naïve infants resulted in observations of enhanced respiratory disease (ERD) following subsequent natural RSV infection in vaccinees. In these studies, infants immunized with FI-RSV had higher rates of severe RSV disease compared with controls. This outcome redirected focus on identifying the immunologic mechanisms that precipitated ERD as a prerequisite to further vaccine development. Improved understanding of the immunopathogenesis of ERD derived from animal models has stimulated development of new candidate vaccines and engendered discussions among RSV experts about the safety data needed to advance these products into the clinic, and ultimately, into the target population of RSV-naïve infants. The recognition that multiple products would soon be ready for testing in infants and children prompted the FDA to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to seek perspectives and advice of experts regarding the types and extent of preclinical and clinical data that might be needed to support testing in RSV-naïve infants for specific types of candidate RSV vaccines. Committee members agreed that, if certain conditions are met in preclinical and early clinical studies, it would be reasonable to move forward from studies in adults and older children and into clinical trials evaluating vaccine safety and efficacy in RSV-naïve infants. Herein, we review and summarize perspectives on the discussion regarding recommendations for RSV vaccine development in this population.


Assuntos
Imunização , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vírus Sincicial Respiratório Humano/imunologia , Comitês Consultivos , Animais , Produtos Biológicos/administração & dosagem , Pré-Escolar , Modelos Animais de Doenças , Humanos , Lactente , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Índice de Gravidade de Doença
4.
PLoS One ; 14(8): e0220780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415584

RESUMO

Measles virus is highly infectious and remains a leading cause of vaccine preventable deaths in children. Neutralizing antibody responses elicited by measles virus infection or immunization are a serological correlate of protection. We describe a high-throughput neutralization assay to improve surveillance for measles immunity. Measles virus-antibody mixtures were incubated on Vero cell monolayers and 24 hours later cell-lysates harvested and subjected to one-step SYBR green RT-qPCR to amplify a target sequence within the measles virus nucleoprotein gene. Neutralization endpoint titers were interpolated to determine the dilution that inhibited the relative amplicon copy number by at least 90% compared to the mean signal obtained in virus control wells in the absence of serum. Anti-measles virus and anti-measles hemagglutinin antisera specifically neutralized measles virus in the microneutralization RT-qPCR assay while pre-immune sera and sera raised against other viruses did not. The microneutralization RT-qPCR assay obeyed the Percentage Law for measles virus inputs ranging from 100-5000 TCID50/well. The linear range of the assay corresponds to measles antibody concentrations of 30 to 3000 mIU/mL. Bland-Altman analysis and two-way analysis of variance demonstrated that results obtained using the microneutralization RT-qPCR assay were comparable to those obtained using a plaque reduction neutralization test and correctly identified human serum samples that were seropositive (95% and 100%, sensitivity and specificity, respectively). Furthermore, these comparisons suggest that a concentration of 300 mIU/mL may be a conservative cut-point to use to identify individuals likely to be protected against severe measles disease when the endpoint is based on 90% inhibition of virus replication. Measles virus microneutralization RT-qPCR is a rapid, sensitive, specific, and robust assay for detecting measles neutralizing antibodies that may help to improve immunization strategies nationally and achieve measles elimination globally.


Assuntos
Anticorpos Neutralizantes/análise , Ensaio de Imunoadsorção Enzimática , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Animais , Chlorocebus aethiops , Humanos , Sarampo/diagnóstico , Sarampo/imunologia , Testes de Neutralização/métodos , Vigilância da População , Sensibilidade e Especificidade , Células Vero
5.
Vaccine ; 34(41): 4843-4849, 2016 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-27566900

RESUMO

Respiratory syncytial virus (RSV) is the most common cause of serious acute lower respiratory illness in infants and young children and a significant cause of disease burden in the elderly and immunocompromised. There are no licensed RSV vaccines to address this significant public health need. While advances in vaccine technologies have led to a recent resurgence in RSV vaccine development, the immune correlates of protection against RSV and the immunology of vaccine-associated enhanced respiratory disease (ERD) remain poorly understood. FDA's Center for Biologics Evaluation and Research (CBER) and NIH's National Institute of Allergy and Infectious Diseases (NIAID) organized and co-sponsored an RSV Vaccines Workshop in Bethesda, Maryland on June 1 and 2, 2015. The goal of the conference was to convene scientists, regulators, and industry stakeholders to discuss approaches to RSV vaccine development within the context of three target populations - infants and children, pregnant women, and individuals >60years of age. The agenda included topics related to RSV vaccine development in general, as well as considerations specific to each target population, such as clinical and serological endpoints. The meeting focused on vaccine development for high income countries (HIC), because issues relevant to vaccine development for low and middle income countries (LMIC) have been discussed in other forums. This manuscript summarizes the discussion of clinical, scientific, and regulatory perspectives, research gaps, and lessons learned.


Assuntos
Pesquisa Biomédica , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Idoso , Animais , Pré-Escolar , Ensaios Clínicos como Assunto , Congressos como Assunto , Feminino , Humanos , Lactente , Maryland , National Institutes of Health (U.S.) , Gravidez , Vírus Sincicial Respiratório Humano , Estados Unidos , United States Food and Drug Administration
7.
J Virol ; 88(9): 5100-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24574396

RESUMO

UNLABELLED: The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5.RSV-F) and the protection provided following immunization with Ad5.RSV-F and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given i.m. or i.n., and these responses correlated with reduced replication of the virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5.RSV-F at 1 × 10(11) viral particles (v.p.) elicited antibody titers 64- to 256-fold greater than those seen after natural infection. CRs boosted with Ad5.RSV-F i.n. 28 days after an i.m. dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F-protein antigenic sites revealed substantial differences between antibodies elicited by Ad5.RSV-F and those seen after RSV infection; differences in antibody profiles were also seen between CRs given Ad5.RSV-F i.m. and CRs given Ad5.RSV-F i.n. Ad5.RSV-F priming did not result in enhanced disease following live-virus challenge, in contrast to the histopathology seen in CRs given the formalin-inactivated RSV/A/Burnett vaccine. IMPORTANCE: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in infants and young children and a serious health threat in the immunocompromised and the elderly. Infection severity increased in children in an immunization trial, hampering the over 4-decade-long quest for a successful RSV vaccine. In this study, we show that a genetically engineered RSV-F-encoding adenoviral vector provides protective immunity against RSV challenge without enhanced lung disease in cotton rats (CRs). CRs were vaccinated under a number of different regimens, and the immunity induced by the recombinant adenoviral RSV vaccine administered by use of an intramuscular prime-intranasal boost regimen may provide the best protection for young infants and children at risk of RSV infection, since this population is naive to adenoviral preformed immunity. Overall, this report describes a potential RSV vaccine candidate that merits further evaluation in a phase I clinical study in humans.


Assuntos
Adenoviridae/genética , Portadores de Fármacos , Vetores Genéticos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Injeções Intramusculares , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/genética , Sigmodontinae , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/imunologia
8.
Clin Vaccine Immunol ; 21(3): 383-90, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24403526

RESUMO

The nucleoprotein of respiratory syncytial virus (RSV-N) is immunogenic and elicits an IgG response following infection. The RSV-N gene was cloned into a mammalian expression vector, pREN2, and the expressed luciferase-tagged protein (Ruc-N) detected anti-RSV-N-specific IgG antibodies using a high-throughput immunoprecipitation method (the luciferase immunoprecipitation system [LIPS]-N(RSV) assay). The specificity of the assay was evaluated using monoclonal antibodies (MAbs) and monospecific pre- and postimmunization rabbit antisera. Blood serum samples from chimpanzees and humans with proven/probable RSV infection were also tested. The pre- and postimmunization serum samples from rabbits given human metapneumovirus (HMPV) or measles virus were negative when tested by the LIPS-N(RSV) assay, while antisera obtained after immunization with either the RSV-A or RSV-B strain gave positive signals in a dose-dependent manner. RSV-N MAb 858-3 gave a positive signal in the LIPS-N(RSV) assay, while MAbs against other paramyxovirus nucleoproteins or RSV-F or RSV-G did not. Serum samples from chimpanzees simultaneously immunized with vaccinia-RSV-F and vaccinia-RSV-G recombinant viruses were negative in the LIPS-N(RSV) assay; however, anti-RSV-N IgG responses were detected following subsequent RSV challenge. Seven of the 12 infants who were seronegative at 9 months of age had detectable anti-RSV-N antibodies when they were retested at 15 to 18 months of age. The LIPS-N(RSV) assay detects specific anti-RSV-N IgG responses that may be used as a biomarker of RSV infection.


Assuntos
Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoprecipitação/métodos , Luciferases/análise , Nucleoproteínas/imunologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/imunologia , Animais , Antígenos Virais/imunologia , Humanos , Lactente , Pan troglodytes , Coelhos , Sensibilidade e Especificidade , Proteínas Virais/imunologia
9.
Microb Pathog ; 55: 9-15, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23247146

RESUMO

Respiratory viral infections in infants and young children frequently cause illness that can easily progress to hospitalization and death. There are currently no licensed vaccines to prevent respiratory viral disease in children younger than 6 months, reflecting safety concerns and the difficulty in inducing effective immune responses in infants. This review discusses vaccines that have been developed, or are currently being developed, against influenza and respiratory syncytial virus, with a focus on studies performed to demonstrate their safety and efficacy, and the impact of immunologic immaturity and maternal antibodies on the infant response to vaccines.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Orthomyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Animais , Humanos , Lactente , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Influenza Humana/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem
10.
J Infect Dis ; 206(4): 512-22, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22693229

RESUMO

BACKGROUND: Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). METHODS: HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. RESULTS: At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. CONCLUSIONS: Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. CLINICAL TRIALS REGISTRATION: NCT00013871 (www.clinicaltrials.gov).


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Imunização Secundária/métodos , Memória Imunológica , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Feminino , HIV-1/isolamento & purificação , Humanos , Lactente , Masculino , Vacina contra Sarampo/administração & dosagem , Testes de Neutralização , Carga Viral , Ensaio de Placa Viral
11.
J Infect Dis ; 204(3): 426-32, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21742842

RESUMO

BACKGROUND: A 30-second aerosol measles vaccination successfully primes children 12 months of age and older but is poorly immunogenic when given to 9-month-old children. We examined the immune responses when increasing the duration to aerosol exposure in 9-month-olds. METHODS: One hundred and thirteen healthy 9-month-old children from Mexico City were enrolled; 58 received aerosol EZ measles vaccine for 2.5 minutes and 55 subcutaneously. Measles-specific neutralizing antibodies and cellular responses were measured before and at 3 and 6 months postimmunization. RESULTS: Adaptive immunity was induced in 97% after aerosol and 98% after subcutaneous administration. Seroconversion rates and GMCs were 95% and 373 mIU/mL (95% confidence interval [CI], 441-843) following aerosol vaccination and 91% and 306 mIU/mL (95% CI, 367-597) after subcutaneous administration at 3 months. The percentage of children with a measles-specific stimulation index ≥3 was 45% and 60% in the aerosol versus 55% and 59% in the subcutaneous group at 3 and 6 months, respectively. CD8 memory cell frequencies were higher in the aerosol group at 3 months compared with the subcutaneous group. Adverse reactions were comparable in both groups. CONCLUSIONS: Increasing exposure time to aerosol measles vaccine elicits immune responses that are comparable to those seen when an equivalent dose is administered by the subcutaneous route in 9-month-old infants.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Sarampo/administração & dosagem , Vacinação , Imunidade Adaptativa , Aerossóis , Feminino , Humanos , Lactente , Interferon gama/biossíntese , Ativação Linfocitária , Masculino , Vacina contra Sarampo/imunologia , México , Linfócitos T/imunologia , Fatores de Tempo
12.
J Infect Dis ; 204 Suppl 1: S549-58, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21666212

RESUMO

Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques.


Assuntos
Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vírus do Sarampo/classificação , Sarampo/imunologia , Adolescente , Distribuição por Idade , Anticorpos Neutralizantes , Anticorpos Antivirais/sangue , Afinidade de Anticorpos , Biomarcadores , Criança , Pré-Escolar , Humanos , Imunoglobulina M/sangue , Imunoprecipitação , Lactente , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vírus do Sarampo/imunologia , Estados Unidos/epidemiologia , Adulto Jovem
13.
Vaccine ; 26(38): 4877-8, 2008 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-18586062

RESUMO

The prevalence of antibodies to measles, mumps, and rubella in US military recruits is of importance to public health leaders. We performed ELISA testing using a commercially available product on samples from 537 recruits obtained in 1998, of which 437 were positive (81%). We then performed a validation study in a subsample of the population using plaque reduction neutralization (PRN) to assess misclassification error. This resulted in a corrected estimate of the prevalence of immunity to measles of 96% (95% CI: 92-100%). The military vaccinates a percentage of recruits who are likely to be immune if more sensitive testing, such as PRN, was used.


Assuntos
Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Sarampo/diagnóstico , Sarampo/imunologia , Militares , Ensaio de Imunoadsorção Enzimática/normas , Humanos , Sarampo/epidemiologia , Vírus do Sarampo/imunologia , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Vacinação
14.
Clin Infect Dis ; 45(11): 1417-24, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17990222

RESUMO

BACKGROUND: The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus. METHODS: Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations. RESULTS: Neutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/mL. CONCLUSIONS: Infants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/transmissão , Vírus do Sarampo/imunologia , Adulto , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunidade Materno-Adquirida , Lactente , Transmissão Vertical de Doenças Infecciosas , Masculino , Gravidez , Complicações Infecciosas na Gravidez , Zâmbia/epidemiologia
15.
J Infect Dis ; 196(3): 347-55, 2007 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-17597448

RESUMO

BACKGROUND: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination. METHODS: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia. RESULTS: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. CONCLUSIONS: Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/imunologia , Vacina contra Sarampo/imunologia , Sarampo/prevenção & controle , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunização Secundária , Lactente , Masculino , Sarampo/complicações , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Zâmbia/epidemiologia
16.
Pediatrics ; 119(3): e574-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17332177

RESUMO

OBJECTIVE: Extremely preterm infants mount lower antibody responses than term infants to several vaccines. The objective of this study was to measure the immunogenicity of measles-mumps-rubella and varicella vaccines in preterm and term children. METHODS: Immune status before immunization and immune response after immunization with measles-mumps-rubella and varicella vaccines at 15 months of age were compared in 32 infants, 16 of whom were preterm (< 29 weeks' gestation) and 16 of whom were term (> or = 37 weeks' gestation) at birth. Blood was drawn before vaccination and 3 to 6 weeks thereafter. Measles antibody was measured by plaque reduction neutralization assay. Mumps and rubella immunoglobulin G were measured in available sera by enzyme-linked fluorescent immunoassay. Varicella immunoglobulin G was measured in available sera by glycoprotein enzyme-linked immunosorbent assay. Values that were above or below the assay limits were assigned values double or half those limits, respectively. The primary outcome was the geometric mean antibody titer. RESULTS: Preterm children had lower mumps and rubella geometric mean titers than did term children before vaccine, and nearly all children were seronegative for each of the 4 vaccine antigens before immunization. Measles, mumps, rubella, and varicella geometric mean titers were similar between groups after vaccine. All children were seropositive for measles after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children were seropositive for varicella. CONCLUSIONS: Preterm children mounted antibody responses that were similar to those of term children after measles-mumps-rubella and varicella vaccines at 15 months of age.


Assuntos
Vacina contra Varicela/imunologia , Recém-Nascido de Peso Extremamente Baixo ao Nascer/imunologia , Recém-Nascido Prematuro/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Herpesvirus Humano 3/imunologia , Humanos , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer/sangue , Recém-Nascido , Recém-Nascido Prematuro/sangue , Vírus do Sarampo/imunologia , Vírus da Caxumba/imunologia , Valores de Referência , Vírus da Rubéola/imunologia
17.
J Virol ; 81(1): 261-71, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17050595

RESUMO

It has been shown previously that the fusion glycoprotein of human respiratory syncytial virus (RSV-F) interacts with cellular heparan sulfate. Synthetic overlapping peptides derived from the F-protein sequence of RSV subtype A (strain A2) were tested for their ability to bind heparin using heparin-agarose affinity chromatography (HAAC). This evaluation identified 15 peptides representing eight linear heparin-binding domains (HBDs) located within F1 and F2 and spanning the protease cleavage activation site. All peptides bound to Vero and A549 cells, and binding was inhibited by soluble heparins and diminished by either enzymatic treatment to remove cell surface glycosaminoglycans or by treatment with sodium chlorate to decrease cellular sulfation. RSV-F HBD peptides were less likely to bind to glycosaminoglycan-deficient CHO-745 cells than parental CHO-K1 cells that express these molecules. Three RSV-F HBD peptides (F16, F26, and F55) inhibited virus infectivity; two of these peptides (F16 and F55) inhibited binding of virus to Vero cells, while the third (F26) did not. These studies provided evidence that two of the linear HBDs mapped by peptides F16 and F55 may mediate one of the first steps in the attachment of virus to cells while the third, F26, inhibited infectivity at a postattachment step, suggesting that interactions with cell surface glycosaminoglycans may play a role in infectivity of some RSV strains.


Assuntos
Heparina/metabolismo , Peptídeos/farmacologia , Vírus Sincicial Respiratório Humano/patogenicidade , Proteínas Virais de Fusão/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Células CHO , Cloratos/farmacologia , Chlorocebus aethiops , Cricetinae , Cricetulus , Produtos do Gene gag/genética , Produtos do Gene gag/metabolismo , Glicoproteínas/química , Glicoproteínas/metabolismo , Humanos , Liases/farmacologia , Dados de Sequência Molecular , Mapeamento de Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/metabolismo , Células Vero , Proteínas Virais de Fusão/metabolismo
18.
J Infect Dis ; 194(6): 781-9, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16941344

RESUMO

Measles infection induces lifelong immunity; however, wild-type infection stimulates higher levels of measles-virus-neutralizing antibodies (mnAbs) than does vaccination. Because the proportion of the donor population with vaccine-induced measles immunity is increasing, this study was conducted to determine whether this shift in demographic characteristics affects mnAb levels in contemporary lots of Immune Globulin Intravenous (Human) (IGIV). When 166 lots of 7 IGIV products manufactured between 1998 and 2003 were assayed by plaque-reduction neutralization test, there was a progressive decrease in geometric mean titers in lots manufactured between 1999 and 2002. IGIV products manufactured from recovered plasma had significantly higher titers than did those manufactured from Source Plasma, which could reflect a change in donor demographic characteristics, because Source Plasma donors tend to be much younger. A reduction in mnAbs also correlated with the loss of either IgG1 and IgG3, possibly because of certain manufacturing procedures, or bivalent antibodies (i.e., intact IgG and F(ab')2), because of fragmentation.


Assuntos
Anticorpos Antivirais/análise , Imunoglobulina G/imunologia , Imunoglobulinas Intravenosas/imunologia , Vírus do Sarampo/imunologia , Estudos de Avaliação como Assunto , Humanos , Imunoglobulina G/análise , Imunoglobulinas Intravenosas/análise , Testes de Neutralização , Fatores de Tempo
19.
J Virol ; 80(10): 5032-40, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16641294

RESUMO

The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [(3)H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with MAb against either of its receptor chains, IFN-lambdaR1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons.


Assuntos
Antivirais/farmacologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Citocinas/fisiologia , Terapia de Imunossupressão , Interferon-alfa/fisiologia , Interleucinas/fisiologia , Vírus Sincicial Respiratório Humano/imunologia , Adulto , Antígenos de Bactérias/farmacologia , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Proliferação de Células , Sistema Livre de Células/imunologia , Citocinas/metabolismo , Citocinas/farmacologia , Citomegalovirus/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Sinergismo Farmacológico , Enterotoxinas/farmacologia , Humanos , Interferon-alfa/farmacologia , Interferons , Interleucinas/farmacologia , Monócitos/imunologia , Monócitos/metabolismo
20.
Vaccine ; 24(5): 683-90, 2006 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16154241

RESUMO

UNLABELLED: Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children. METHODS: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed. RESULTS: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06). CONCLUSIONS: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.


Assuntos
Anticorpos Antivirais/biossíntese , Vacina contra Sarampo/imunologia , Sarampo/prevenção & controle , Aerossóis , Formação de Anticorpos/imunologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunidade Celular/imunologia , Imunização , Lactente , Injeções Subcutâneas , Interferon gama/biossíntese , Masculino , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/efeitos adversos , México , Linfócitos T/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Ensaio de Placa Viral
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