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1.
Mol Ther ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38981468

RESUMEN

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene. This combinatorial approach achieved correction of ornithine transcarbamylase deficiency in the neonatal Spfash mouse model following a single delivery to dividing hepatocytes in the newborn liver. Correction remained stable into adulthood, while a conventional rAAV approach resulted in a return to the disease state. In non-human primates, integration by transposition, mediated by this technology, improved gene expression 10-fold over conventional rAAV-mediated gene transfer while requiring 5-fold less vector. Additionally, integration site analysis confirmed a random profile while specifically targeting TA dinucleotides across the genome. Together, these findings demonstrate that transposable elements can improve rAAV-delivered therapies by lowering the vector dose requirement and associated toxicity while expanding target cell types.

2.
J Biomed Mater Res A ; 111(9): 1309-1321, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36932841

RESUMEN

Cardiovascular disease is the leading cause of death in the United States, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI), scar tissue formation in the myocardium, and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplantation. An alternative to total-organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch. Acellular cardiac patches have previously been investigated using synthetic or decellularized native materials to improve cardiac function. However, a limitation of this strategy is that acellular cardiac patches only reshape the ventricle and do not increase cardiac contractile function. Toward the development of a cardiac patch, our laboratory previously developed a cell-populated composite fibrin scaffold and aligned microthreads to recapitulate the mechanical properties of native myocardium. In this study, we explore micropatterning the surfaces of fibrin gels to mimic anisotropic native tissue architecture and promote cellular alignment of human induced pluripotent stem cell cardiomyocytes (hiPS-CM), which is crucial for increasing scaffold contractile properties. hiPS-CMs seeded on micropatterned surfaces exhibit cellular elongation, distinct sarcomere alignment, and circumferential connexin-43 staining at 14 days of culture, which are necessary for mature contractile properties. Constructs were also subject to electrical stimulation during culture to promote increased contractile properties. After 7 days of stimulation, contractile strains of micropatterned constructs were significantly higher than unpatterned controls. These results suggest that the use of micropatterned topographic cues on fibrin scaffolds may be a promising strategy for creating engineered cardiac tissue.


Asunto(s)
Insuficiencia Cardíaca , Células Madre Pluripotentes Inducidas , Humanos , Miocitos Cardíacos , Ingeniería de Tejidos/métodos , Fibrina , Células Madre Pluripotentes Inducidas/metabolismo , Miocardio , Insuficiencia Cardíaca/metabolismo , Andamios del Tejido
3.
J Hum Nutr Diet ; 36(4): 1406-1416, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36793238

RESUMEN

BACKGROUND: Nutrition professionals function at the nexus of food, nutrition status and the myriad of determinants influencing these. However, defining our role in food system transformation requires a multifaceted and deep understanding of sustainability in the context of nutrition and dietetics (N&D). Practitioner perspectives and experiences provide a rich source of practice wisdom that can inform authentic curriculum to equip students for the complex realities of practice; however, there is limited understanding of these in the Australian higher education setting. METHODS: Qualitative methodology using semistructured interviews with 10 Australian N&D professionals. Thematic analysis was used to understand how they perceive opportunities and barriers for integrating sustainability into practice. RESULTS: Practitioners' experience in sustainability practice varied. Themes were identified in two categories: opportunities and barriers. Themes that reflected future practice opportunities included "Preparing the workforce" (for academics and practitioners interfacing with students), "Practical individual level work" and "System level and policy interests". Themes that were considered barriers to integrating sustainability in practice included "lack of contextual evidence" and "complexity and competing priorities". CONCLUSIONS: Our findings make a novel contribution to the current literature as we recognise practitioners as a source of experience anticipating where sustainability and nutrition practice intersect. Our work provides practice-informed content and context that may assist educators to create authentic sustainability-focused curriculum and assessment to replicate the complexity of practice.


Asunto(s)
Estado Nutricional , Estudiantes , Humanos , Australia , Curriculum , Políticas
4.
PLoS Biol ; 20(4): e3001604, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35436284

RESUMEN

Cryptosporidium is a leading infectious cause of diarrhea around the world associated with waterborne outbreaks, community spread, or zoonotic transmission. The parasite has significant impact on early childhood mortality, and infection is both a consequence and cause of malnutrition and stunting. There is currently no vaccine, and treatment options are very limited. Cryptosporidium is a member of the Apicomplexa, and, as typical for this, protist phylum relies on asexual and sexual reproduction. In contrast to other Apicomplexa, including the malaria parasite Plasmodium, the entire Cryptosporidium life cycle unfolds in a single host in less than 3 days. Here, we establish a model to image life cycle progression in living cells and observe, track, and compare nuclear division of asexual and sexual stage parasites. We establish the length and sequence of the cell cycles of all stages and map the developmental fate of parasites across multiple rounds of invasion and egress. We propose that the parasite executes an intrinsic program of 3 generations of asexual replication, followed by a single generation of sexual stages that is independent of environmental stimuli. We find no evidence for a morphologically distinct intermediate stage (the tetraploid type II meront) but demonstrate direct development of gametes from 8N type I meronts. The progeny of each meront is collectively committed to either asexual or sexual fate, but, importantly, meronts committed to sexual fate give rise to both males and females. We define a Cryptosporidium life cycle matching Tyzzer's original description and inconsistent with the coccidian life cycle now shown in many textbooks.


Asunto(s)
Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Animales , Preescolar , Criptosporidiosis/parasitología , Femenino , Células Germinativas , Humanos , Estadios del Ciclo de Vida , Masculino
5.
Acad Emerg Med ; 29(4): 442-455, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34962682

RESUMEN

BACKGROUND: Emergency department (ED) patients with nonfatal opioid overdose are at high risk for subsequent fatal overdose, yet ED programs aimed at reducing harm from opioid use remain underdeveloped. OBJECTIVES: The objective was to pilot a statewide ED take-home naloxone program and improve the care of patients with opioid use disorder (OUD) and risky drug use through training and interprofessional network building. METHODS: Nine hospital EDs with pharmacy, nurse, and physician champions were recruited, surveyed, and trained. Take-home naloxone rescue kits were developed, disseminated, and tracked. Two overdose prevention summits were convened prior to the COVID pandemic, and two X-waiver training courses aimed at emergency physicians and advanced practice providers were arranged, both in person and virtual. RESULTS: A total of 872 naloxone rescue kits were distributed to ED patients at risk of opioid overdose during the first phase of this project, and more than 140 providers were trained in the use of medications for OUD in acute care settings. CONCLUSIONS: A statewide ED take-home naloxone program was shown to be feasible across a range of different hospitals with varying maturity in preexisting OUD resources and capabilities. Future work will be aimed at both expanding and measuring the effectiveness of this work.


Asunto(s)
COVID-19 , Sobredosis de Droga , Sobredosis de Opiáceos , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/prevención & control , Servicio de Urgencia en Hospital , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/prevención & control , Calidad de la Atención de Salud
6.
Trends Parasitol ; 36(6): 495-498, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32407679

RESUMEN

In an ideal world, there are equal opportunities for women to enter and progress in all scientific disciplines without bias or prejudice. Here, we share our experiences in building communities of women parasitology and offer easy-to-implement guidelines for scientists and institutions to overcome unconscious bias and create environments with better gender equality and diversity.


Asunto(s)
Relaciones Interpersonales , Personal de Laboratorio/estadística & datos numéricos , Parasitología/organización & administración , Prejuicio/prevención & control , Diversidad Cultural , Humanos , Parasitología/estadística & datos numéricos , Parasitología/tendencias , Selección de Personal/normas
7.
Infect Immun ; 88(4)2020 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-32014892

RESUMEN

Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. "Immediate" IFN-γ and IL-12p40 production was not detected in MyD88-/- mice. However, unlike IL-12p40-/- and IFN-γ-/- mice, MyD88-/- mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88-/- mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-γ production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.


Asunto(s)
Coccidiosis/inmunología , Factores Inmunológicos/metabolismo , Interferón gamma/metabolismo , Neospora/inmunología , Enfermedades de los Roedores/inmunología , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Animales , Interferón gamma/deficiencia , Interleucina-12/deficiencia , Interleucina-12/metabolismo , Ratones , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/deficiencia , Factor 88 de Diferenciación Mieloide/metabolismo , Neospora/crecimiento & desarrollo , Análisis de Supervivencia , Factores de Tiempo , Toxoplasma/crecimiento & desarrollo
8.
PLoS Biol ; 17(9): e3000446, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31487278

RESUMEN

Toxoplasma gondii is a remarkably successful protozoan parasite that infects a third of the human population, along with most mammals and birds. However, the sexual portion of the parasite's life cycle is narrowly limited to cats. How parasites distinguish between hosts has long been a mystery. A new study reveals that Toxoplasma identifies cats based on a single fatty acid, linoleic acid. Experimental manipulation of fatty acid metabolism by drug treatment turns a mouse into a cat in the "eye" of the parasite. This new model enables genetic crosses of an important human pathogen without the use of companion animals and opens the door to future discovery.


Asunto(s)
Parásitos , Toxoplasma , Animales , Gatos , Especificidad del Huésped , Humanos , Estadios del Ciclo de Vida , Linoleoil-CoA Desaturasa , Ratones
9.
Nat Microbiol ; 4(12): 2226-2236, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31477896

RESUMEN

The apicomplexan parasite Cryptosporidium is a leading global cause of severe diarrhoeal disease and an important contributor to early childhood mortality. Currently, there are no fully effective treatments or vaccines available. Parasite transmission occurs through ingestion of oocysts, through either direct contact or consumption of contaminated water or food. Oocysts are meiotic spores and the product of parasite sex. Cryptosporidium has a single-host life cycle in which both asexual and sexual processes occur in the intestine of infected hosts. Here, we genetically engineered strains of Cryptosporidium to make life cycle progression and parasite sex tractable. We derive reporter strains to follow parasite development in culture and in infected mice and define the genes that orchestrate sex and oocyst formation through mRNA sequencing of sorted cells. After 2 d, parasites in cell culture show pronounced sexualization, but productive fertilization does not occur and infection falters. By contrast, in infected mice, male gametes successfully fertilize female parasites, which leads to meiotic division and sporulation. To rigorously test for fertilization, we devised a two-component genetic-crossing assay using a reporter that is activated by Cre recombinase. Our findings suggest obligate developmental progression towards sex in Cryptosporidium, which has important implications for the treatment and prevention of the infection.


Asunto(s)
Criptosporidiosis/parasitología , Cryptosporidium parvum/crecimiento & desarrollo , Cryptosporidium parvum/genética , Estadios del Ciclo de Vida/fisiología , Desarrollo Sexual/fisiología , Animales , Cryptosporidium parvum/citología , Modelos Animales de Enfermedad , Femenino , Fertilización , Expresión Génica , Genes Protozoarios/genética , Proteínas de Homeodominio/genética , Interferón gamma/genética , Masculino , Ratones , Ratones Noqueados , Oocistos , Análisis de Secuencia de ARN
10.
mSphere ; 3(5)2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30333181

RESUMEN

The opportunistic intracellular parasite Toxoplasma gondii causes a lifelong chronic infection capable of reactivating in immunocompromised individuals, which can lead to life-threatening complications. Following invasion of the host cell, host mitochondria associate with the parasitophorous vacuole membrane. This phenotype is T. gondii strain specific and is mediated by expression of a host mitochondrial association-competent (HMA+) paralog of the parasite protein mitochondrial association factor 1 (MAF1b). Previous work demonstrated that expression of MAF1b in strains that do not normally associate with host mitochondria increases their fitness during acute infection in vivo However, the impact of MAF1b expression during chronic T. gondii infection is unclear. In this study, we assess the impact of MAF1b expression on cyst formation and cytokine production in mice. Despite generally low numbers of cysts generated by the in vitro culture-adapted strains used in this study, we find that parasites expressing MAF1b have higher numbers of cysts in the brains of chronically infected mice and that MAF1b+ cyst burden significantly increases during the course of chronic infection. Consistent with this, mice infected with MAF1b+ parasites have higher levels of the serum cytokines RANTES and VEGF (vascular endothelial growth factor) at day 57 postinfection, although this could be due to higher parasite burden at this time point rather than direct manipulation of these cytokines by MAF1b. Overall these data indicate that MAF1b expression may also be important in determining infection outcome during the chronic phase, either by directly altering the cytokine/signaling environment or by increasing proliferation during the acute and/or chronic phase.IMPORTANCE The parasite Toxoplasma gondii currently infects approximately one-third of the world's population and causes life-threatening toxoplasmosis in individuals with undeveloped or weakened immune systems. Current treatments are unable to cure T. gondii infection, leaving infected individuals with slow-growing tissue cysts for the remainder of their lives. Previous work has shown that expression of the parasite protein mitochondrial association factor 1 (MAF1b) is responsible for the association of T. gondii parasites with host mitochondria and provides a selective advantage during acute infection. Here we examine the impact of MAF1b expression during chronic T. gondii infection. We find that mice infected with MAF1b-expressing parasites have higher cyst burden and cytokine levels than their wild-type counterparts. A better understanding of the genes involved in establishing and maintaining chronic infection will aid in discovering effective therapeutics for chronically infected individuals.


Asunto(s)
Interacciones Huésped-Parásitos , Proteínas Mitocondriales/genética , Proteínas Protozoarias/genética , Toxoplasma/genética , Toxoplasma/patogenicidad , Toxoplasmosis Cerebral/parasitología , Animales , Encéfalo/patología , Quimiocina CCL5/sangre , Enfermedad Crónica , Quistes/metabolismo , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Toxoplasmosis Cerebral/sangre , Factor A de Crecimiento Endotelial Vascular/sangre
11.
J Biol Chem ; 293(29): 11470-11480, 2018 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-29899118

RESUMEN

Signaling activated by binding of the CXC motif chemokine ligand 12 (CXCL12) to its cognate G protein-coupled receptor (GPCR), chemokine CXC motif receptor 4 (CXCR4), is linked to metastatic disease. However, the mechanisms governing CXCR4 signaling remain poorly understood. Here, we show that endocytosis and early endosome antigen 1 (EEA1), which is part of the endosome fusion machinery, are required for CXCL12-mediated AKT Ser/Thr kinase (Akt) signaling selective for certain Akt substrates. Pharmacological inhibition of endocytosis partially attenuated CXCL12-induced phosphorylation of Akt, but not phosphorylation of ERK-1/2. Similarly, phosphorylation of Akt, but not ERK-1/2, stimulated by CXCL13, the cognate ligand for the chemokine receptor CXCR5, was also attenuated by inhibited endocytosis. Furthermore, siRNA-mediated depletion of the Rab5-effector EEA1, but not of adaptor protein, phosphotyrosine-interacting with PH domain and leucine zipper 1 (APPL1), partially attenuated Akt, but not ERK-1/2, phosphorylation promoted by CXCR4. Attenuation of Akt phosphorylation through inhibition of endocytosis or EEA1 depletion was associated with reduced signaling to Akt substrate forkhead box O1/3a but not the Akt substrates TSC complex subunit 2 or glycogen synthase kinase 3ß. This suggested that endocytosis and endosomes govern discrete aspects of CXCR4- or CXCR5-mediated Akt signaling. Consistent with this hypothesis, depletion of EEA1 reduced the ability of CXCL12 to attenuate apoptosis in suspended, but not adherent, HeLa cells. Our results suggest a mechanism whereby compartmentalized chemokine-mediated Akt signaling from endosomes suppresses the cancer-related process known as anoikis. Targeting this signaling pathway may help inhibit metastatic cancer involving receptors such as CXCR4.


Asunto(s)
Apoptosis , Endocitosis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células HeLa , Humanos , Sistema de Señalización de MAP Quinasas , Fosforilación
12.
Mol Microbiol ; 108(5): 519-535, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29505111

RESUMEN

The Toxoplasma gondii locus mitochondrial association factor 1 (MAF1) encodes multiple paralogs, some of which mediate host mitochondrial association (HMA). Previous work showed that HMA was a trait that arose in T. gondii through neofunctionalization of an ancestral MAF1 ortholog. Structural analysis of HMA-competent and incompetent MAF1 paralogs (MAF1b and MAF1a, respectively) revealed that both paralogs harbor an ADP ribose binding macro-domain, with comparatively low (micromolar) affinity for ADP ribose. Replacing the 16 C-terminal residues of MAF1b with those of MAF1a abrogated HMA, and we also show that only three residues in the C-terminal helix are required for MAF1-mediated HMA. Importantly these same three residues are also required for the in vivo growth advantage conferred by MAF1b, providing a definitive link between in vivo proliferation and manipulation of host mitochondria. Co-immunoprecipitation assays reveal that the ability to interact with the mitochondrial MICOS complex is shared by HMA-competent and incompetent MAF1 paralogs and mutants. The weak ADPr coordination and ability to interact with the MICOS complex shared between divergent paralogs may represent modular ancestral functions for this tandemly expanded and diversified T. gondii locus.


Asunto(s)
Mitocondrias/metabolismo , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Toxoplasma/fisiología , Toxoplasmosis/parasitología , Adenosina Difosfato Ribosa/química , Adenosina Difosfato Ribosa/genética , Adenosina Difosfato Ribosa/metabolismo , Animales , Femenino , Fibroblastos/citología , Fibroblastos/parasitología , Prepucio/citología , Sitios Genéticos , Interacciones Huésped-Parásitos/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Protozoarias/genética , Toxoplasma/genética
13.
Genetics ; 203(1): 283-98, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26920761

RESUMEN

In Toxoplasma gondii, an intracellular parasite of humans and other animals, host mitochondrial association (HMA) is driven by a gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. However, the importance of MAF1 gene duplication in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we used within- and between-species comparative analysis to determine that the MAF1 locus is duplicated in T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative, Neospora caninum Using cross-species complementation, we determined that the MAF1 locus harbors multiple distinct paralogs that differ in their ability to mediate HMA, and that only T. gondii and H. hammondi harbor HMA(+) paralogs. Additionally, we found that exogenous expression of an HMA(+) paralog in T. gondii strains that do not normally exhibit HMA provides a competitive advantage over their wild-type counterparts during a mouse infection. These data indicate that HMA likely evolved by neofunctionalization of a duplicate MAF1 copy in the common ancestor of T. gondii and H. hammondi, and that the neofunctionalized gene duplicate is selectively advantageous.


Asunto(s)
Duplicación de Gen , Interacciones Huésped-Parásitos/genética , Proteínas Protozoarias/genética , Toxoplasma/genética , Toxoplasmosis/parasitología , Animales , Gatos , Dosificación de Gen , Regulación de la Expresión Génica , Ratones , Ratones Noqueados , Familia de Multigenes , Transcripción Genética
14.
Eukaryot Cell ; 13(12): 1507-18, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25280815

RESUMEN

Toxoplasma gondii and its nearest extant relative, Hammondia hammondi, are phenotypically distinct despite their remarkable similarity in gene content, synteny, and functionality. To begin to identify genetic differences that might drive distinct infection phenotypes of T. gondii and H. hammondi, in the present study we (i) determined whether two known host-interacting proteins, dense granule protein 15 (GRA15) and rhoptry protein 16 (ROP16), were functionally conserved in H. hammondi and (ii) performed the first comparative transcriptional analysis of H. hammondi and T. gondii sporulated oocysts. We found that GRA15 and ROP16 from H. hammondi (HhGRA15 and HhROP16) modulate the host NF-κB and STAT6 pathways, respectively, when expressed heterologously in T. gondii. We also found the transcriptomes of H. hammondi and T. gondii to be highly distinct. Consistent with the spontaneous conversion of H. hammondi tachyzoites into bradyzoites both in vitro and in vivo, H. hammondi high-abundance transcripts are enriched for genes that are of greater abundance in T. gondii bradyzoites. We also identified genes that are of high transcript abundance in H. hammondi but are poorly expressed in multiple T. gondii life stages, suggesting that these genes are uniquely expressed in H. hammondi. Taken together, these data confirm the functional conservation of known T. gondii virulence effectors in H. hammondi and point to transcriptional differences as a potential source of the phenotypic differences between these species.


Asunto(s)
Toxoplasma/genética , Secuencia de Bases , Núcleo Celular/metabolismo , Células Cultivadas , Regulación de la Expresión Génica , Genes Protozoarios , Interacciones Huésped-Parásitos , Humanos , Datos de Secuencia Molecular , FN-kappa B/metabolismo , Filogenia , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT6/metabolismo , Transcriptoma
15.
J Infect Dis ; 204(10): 1475-82, 2011 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-21949042

RESUMEN

BACKGROUND: The safety and immunogenicity of live, attenuated influenza vaccine (LAIV) has not been compared to that of the standard trivalent inactivated vaccine (TIV) in children with cancer. METHODS: Randomized study of LAIV versus TIV in children with cancer, age 2-21 years, vaccinated according to recommendations based on age and prior vaccination. Data on reactogenicity and other adverse events and blood and nasal swab samples were obtained following vaccination. RESULTS: Fifty-five eligible subjects (mean age, 10.4 years) received vaccine (28 LAIV/27 TIV). Both vaccines were well tolerated. Rhinorrhea reported within 10 days of vaccination was similar in both groups (36% LAIV vs 33% TIV, P > .999). Ten LAIV recipients shed virus; the latest viral shedding was detected 7 days after vaccination. Immunogenicity data were available for 52 subjects, or 26 in each group. TIV induced significantly higher postvaccination geometric mean titers against influenza A viruses (P < .001), greater seroprotection against influenza A/H1N1 (P = .01), and greater seroconversion against A/H3N2 (P = .004), compared with LAIV. No differences after vaccination were observed against influenza B viruses. CONCLUSIONS: As expected, serum antibody response against influenza A strains were greater with TIV than with LAIV in children with cancer. Both vaccines were well tolerated, and prolonged viral shedding after LAIV was not detected. CLINICAL TRIALS REGISTRATION: NCT00906750.


Asunto(s)
Anticuerpos Antivirales/sangre , Huésped Inmunocomprometido , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Neoplasias/inmunología , Adolescente , Niño , Preescolar , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Gripe Humana/prevención & control , Masculino , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunología , Esparcimiento de Virus , Adulto Joven
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