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1.
Urol Clin North Am ; 47(1): 1-4, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757292

RESUMO

High-risk non-muscle invasive bladder cancer is marked by frequent disease recurrences and risk of stage progression, contributing to high surveillance, treatment-related costs, and patient anxiety. Although the mainstay of high-risk non-muscle invasive bladder cancer clinical management remains transurethral resection followed by intravesical bacillus Calmette-Guérin (BCG), patients who develop BCG-unresponsive disease have few salvage options outside of a radical cystectomy with pelvic lymphadenectomy. This article provides a historical context relevant to the development of the BCG-unresponsive definition, an overview of current clinical trial expectations, and an introduction to this issue of Urologic Clinics.


Assuntos
Vacina BCG/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
2.
Urol Clin North Am ; 47(1): 119-128, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757295

RESUMO

Bacillus Calmette-Guerin (BCG)-refractory high-grade non-muscle-invasive bladder cancer remains a challenging problem. Radical cystectomy is standard of care, but carries significant morbidity. Therefore, there is a need for effective treatments. Previous salvage intravesical therapies have had disappointing results with long-term follow-up; however, a wide array of novel agents is currently under investigation. These include novel combinations of existing intravesical agents, novel modes of delivery such as hyperthermia, viral mediated therapies, and immunotherapy. We review the need for novel treatment with existing agents and their long-term results, and discuss novel intravesical therapies and the data currently available on these therapies.


Assuntos
Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Quimioterapia Combinada , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
3.
Urol Clin North Am ; 47(1): 15-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757296

RESUMO

Disease progression and recurrence are common among patients on Bacillus Calmette-Guérin (BCG) therapy, and options for bladder-preserving subsequent therapy remain limited. Ongoing efforts to develop better second-line bladder-sparing therapies rely on clinical trials of patients deemed to have failed management with BCG. This article describes historical definitions of BCG failure, as well as recent efforts to better delineate and refine the clinical criteria for identifying individual patients who will not benefit from further intravesical BCG therapy. It also reviews guidance from the most recent expert consensus panels and professional association guidelines regarding which patients should not receive additional BCG therapy.


Assuntos
Vacina BCG/administração & dosagem , Seleção de Pacientes , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia
4.
Urol Clin North Am ; 47(1): 23-33, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757297

RESUMO

Despite the 40-year reign of bacillus Calmette-Guérin (BCG) as the most effective immunotherapy in urologic cancers, a lack of clinical tools to predict treatment response has hampered progress in the field. Acting as an immunostimulatory agent against a multitude of phenotypically diverse non-muscle-invasive bladder cancers, response to BCG likely depends on both tumor characteristics as well as host factors. With a deeper understanding of the tumor biology as well as the mechanism of action underpinning immunotherapy, newer and more effective clinical tools are being constructed to improve patient selection.


Assuntos
Vacina BCG/administração & dosagem , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Humanos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
5.
Urol Clin North Am ; 47(1): 35-46, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757298

RESUMO

Non-muscle-invasive bladder cancer (NMIBC) is heterogeneous, but current diagnostic and treatment strategies rely primarily on clinical parameters, lacking individualization to tumor and host genetics and biology. The heterogeneity of NMIBCs is derived from mutations, mutation signatures, chromosomal loss, and disruption of molecular pathways, which ultimately affects tumor progression, recurrence, and responsiveness to intravesical and systemic chemotherapy. Although research is still underway, advances in sequencing technology, insight into differential bacillus Calmette-Guérin responses, and new investigational treatment targets will soon offer clinicians new, precision-based tools to risk stratify and determine treatment regimens for future patients with bladder cancer.


Assuntos
Vacina BCG/administração & dosagem , Biomarcadores Tumorais/genética , DNA de Neoplasias/genética , Genômica/métodos , Imunoterapia/métodos , Mutação , Neoplasias da Bexiga Urinária/genética , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA , Progressão da Doença , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
6.
Urol Clin North Am ; 47(1): 47-54, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757299

RESUMO

Despite therapy with intravesical Bacillus Calmette-Guérin, roughly 50% of patients with high-risk non-muscle-invasive bladder cancer will recur. Although cystectomy is the oncologic gold standard in BCG unresponsive disease, salvage intravesical therapies are valuable treatment options that aim to preserve quality of life while decreasing the risk of cancer recurrence and progression. Single-agent intravesical chemotherapy has been a mainstay salvage treatment and foundational to future trials of combination therapy. Treatment with Bacillus Calmette-Guérin derivative therapies has shown promise with response rates comparable with those of single agent chemotherapy and may warrant further investigation in the continued climate of Bacillus Calmette-Guérin shortages.


Assuntos
Vacina BCG/administração & dosagem , Desoxicitidina/análogos & derivados , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Progressão da Doença , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
7.
Urol Clin North Am ; 47(1): 5-13, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757300

RESUMO

The best predictors of response to intravesical immunotherapy are tumor grade and stage, tumor recurrence pattern, nomograms, panels of urinary cytokines, and fluorescent in situ hybridization patterns of urine cytology examinations. Future investigations on predictors of Bacillus Calmette-Guérin efficacy are needed to better select those patients who will really benefit from a conservative treatment. Hardly any of the proposed nomograms were designed to precisely predict the outcome of Bacillus Calmette-Guérin immunotherapy. A new nomogram for NMIBC recurrence and progression based on all non-muscle-invasive bladder cancer subgroups would include factors already proven in cancer prognosis and prediction.


Assuntos
Vacina BCG/administração & dosagem , Imunoterapia/métodos , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Nomogramas , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
8.
Urol Clin North Am ; 47(1): 83-91, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757303

RESUMO

After Bacillus Calmette-Guerin (BCG) failure, there is likely a 6- to 24-month window whereby salvage intravesical therapy might allow for preservation of the bladder without disease worsening. Combination intravesical, salvage therapy for nonmuscle invasive bladder cancer represents a promising avenue for treatment in patients unfit or unwilling to undergo cystectomy. BCG with concomitant immune stimulating agents or immune checkpoint inhibitors, combination chemotherapy regimens, such as gemcitabine and docetaxol, and novel agents currently in clinical trials provide hope for a bladder-sparing alternative for patients after BCG failure.


Assuntos
Vacina BCG/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos , Administração Intravesical , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Quimioterapia Combinada , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
9.
Exp Parasitol ; 207: 107789, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669169

RESUMO

American visceral leishmaniasis is caused by the protozoan Leishmania infantum. The control of the disease depends on the magnitude of the Th1 cell response and IL-10 producing regulatory T cells. Administration of chemokine, such as CXCL10, has shown promising results in the leishmaniasis treatment. Previous studies from our group have shown that CXCL10 induces a reduction in parasite burden in the spleen and a decrease in IL-10 and TGF-ß production in L. infantum-infected BALB/c mice. This work investigated whether CXCL10-treatment reduces IL-10 + Treg cell populations (CD4+CD25+Foxp3+ and Tr1) and induces morphological changes in the spleen. BALB/c mice were infected and treated or not with CXCL10 on the 1st, 3rd and 7th days of infection. CXCL10-treatment was able to reduce the parasite load in the spleen in L. infantum-infected BALB/c mice and this decrease in the number of parasites correlated with the decrease in size of this organ in treated animals compared to untreated animals. 7, 23, and 45 days post-treatment (p.t.), the phenotype and frequency of IL-10 + Treg cells were evaluated by flow cytometry, and the morphological changes of the spleen were analyzed by optical microscopy. After 7 and 23 days p.t., CXCL10-treated animals showed a significant reduction of CD25-Foxp3-IL-10+ (Tr1) cells in the spleen when compared to untreated animals, whereas CD4+CD25+Foxp3+IL-10+ Treg cells reduced later at 23rd and 45th days p.t. Furthermore, while untreated animals showed a significant positive correlation between IL-10 production and Tr1 cells, in CXCL10-treated group this correlation was negative. Thus, these findings show that treatment with CXCL10 chemokine in L. infantum-infected BALB/c mice results in suppression of IL10+ Treg (Foxp3+ and Tr1) cells in the spleen, associated with a reduction in parasite load and splenomegaly.


Assuntos
Quimiocina CXCL10/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Baço/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Adjuvantes Imunológicos/uso terapêutico , Animais , Quimiocina CXCL10/administração & dosagem , Quimiocina CXCL10/farmacologia , Cricetinae , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Humanos , Injeções Intraperitoneais , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/imunologia , Leishmania infantum/patogenicidade , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/imunologia , Carga Parasitária , Baço/parasitologia , Baço/patologia , Linfócitos T Reguladores/imunologia , Virulência
10.
Vet Clin North Am Food Anim Pract ; 35(3): 391-403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590894

RESUMO

Vaccination is a critical tool in modern animal production and key to maintaining animal health. Adjuvants affect the immune response by increasing the rate, quantity, or quality of the protective response generated by the target antigens. Although adjuvant technology dates back to the nineteenth century, there was relatively little improvement in adjuvant technology before the late twentieth century. With the discovery of molecular pathways that regulate the timing, quantity, and quality of the immune response, new technologies are focused on bringing safer, more effective, and inexpensive adjuvants to commercial use.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Doenças dos Animais/prevenção & controle , Ruminantes/imunologia , Vacinação/veterinária , Adjuvantes Imunológicos/farmacologia , Doenças dos Animais/imunologia , Animais
12.
Artigo em Chinês | MEDLINE | ID: mdl-31550770

RESUMO

The number of patients with allergic rhinitis (AR) have been increasing in the world. Establishment of AR model in mice is an important method for the study of this disease. However, there is still no consensus standard for the modeling methods, selection of allergens and adjuvants, and evaluation parameter of AR modeling. Here, we introduce the advancement of AR mouse model in recent years from the above, and provide evidence of references for the standardized process of AR mouse model establishment.


Assuntos
Modelos Animais de Doenças , Rinite Alérgica , Adjuvantes Imunológicos , Animais , Humanos , Camundongos
13.
Eur J Pharm Biopharm ; 145: 1-6, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560955

RESUMO

Both Gram-positive and Gram-negative bacteria can release nano-sized lipid bilayered structures, known as membrane vesicles (MVs). These MVs play an important role in bacterial survival by orchestrating interactions between bacteria and between bacteria and host. The major constituents of MVs are proteins, lipids and nucleic acids. Due to the immunogenicity of the membrane lipids and/or proteins of the MVs, in combination with adjuvant danger signals and the repeating patterns on the nanosized surface, MVs can effectively stimulate the innate and adaptive immune system. Since they are non-replicating, they are safer than attenuated vaccines. In addition, by genetic engineering of the donor cells, further improvements to their safety profile, immunogenicity and yield can be achieved. To date, one MV-based vaccine against Neisseria meningitidis (N. meningitidis) serogroup B was approved. Other (engineered) MVs in the pipeline study are mostly in the preclinical phase.


Assuntos
Bactérias/imunologia , Bicamadas Lipídicas/imunologia , Lipídeos de Membrana/imunologia , Membranas/imunologia , Vacinas/imunologia , Imunidade Adaptativa/imunologia , Adjuvantes Imunológicos , Animais , Formação de Anticorpos/imunologia , Proteínas de Bactérias/imunologia , Humanos
14.
Int J Nanomedicine ; 14: 6601-6613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496701

RESUMO

Purpose: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB). Methods: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1-144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer. Results: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue. Conclusion: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vírus da Hepatite B/metabolismo , Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis/patogenicidade , Sorogrupo , Vírion/metabolismo , Adjuvantes Imunológicos/farmacologia , Sequência de Aminoácidos , Animais , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/ultraestrutura , Citocinas/metabolismo , Escherichia coli/metabolismo , Feminino , Imunidade , Imunização , Inflamação/patologia , Ativação Linfocitária/imunologia , Infecções Meningocócicas/patologia , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/imunologia , Teste Bactericida do Soro , Baço/microbiologia , Linfócitos T/imunologia , Vacinação , Virulência
15.
Cell Physiol Biochem ; 53(3): 496-507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31486324

RESUMO

BACKGROUND/AIMS: Like nucleated cells, erythrocytes (red blood cells, RBCs) are capable of executing programmed cell death pathways. RBCs undergo necroptosis in response to CD59-specific pore-forming toxins (PFTs). The relationship between blood bank storage and RBC necroptosis was explored in this study. METHODS: Human RBCs were stored in standard blood bank additive solutions (AS-1, AS-3, or AS-5) for 1 week and hemolysis was evaluated in the context of necroptosis inhibitors and reactive oxygen species (ROS) scavengers. Activation of key factors including RIP1, RIP3, and MLKL was determined using immunoprecipitations and western blot. RBC vesiculation and formation of echinocytes was determined using phase-contrast microscopy. The effect of necroptosis and storage on RBC clearance was determined using a murine transfusion model. RESULTS: Necroptosis is associated with increased RBC clearance post-transfusion. Moreover, storage in AS-1, AS-3, or AS-5 sensitizes RBCs for necroptosis. Importantly, storage-sensitized RBCs undergo necroptosis in response to multiple PFTs, regardless of specificity for CD59. Storage-sensitized RBCs undergo necroptosis via NADPH oxidase-generated ROS. RBC storage led to RIP1 phosphorylation and necrosome formation in an NADPH oxidase-dependent manner suggesting the basis for this sensitization. In addition, storage led to increased RBC clearance post-transfusion. Clearance of these RBCs was due to Syk-dependent echinocyte formation. CONCLUSION: Storage-induced sensitization to RBC necroptosis and clearance is important as it may be relevant to hemolytic transfusion reactions.


Assuntos
Antígenos CD59/metabolismo , Eritrócitos/citologia , Eritrócitos/metabolismo , Necrose/metabolismo , Adjuvantes Imunológicos , Animais , Apoptose/fisiologia , Bancos de Sangue , Western Blotting , Morte Celular/genética , Morte Celular/fisiologia , Células Cultivadas , Hemólise/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosforilação/genética , Fosforilação/fisiologia , Espécies Reativas de Oxigênio/metabolismo
16.
Medicine (Baltimore) ; 98(33): e16771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415377

RESUMO

The cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 µg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 µg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4 T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.The RD of BCG-CWS was determined to be 100 µg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Esqueleto da Parede Celular/uso terapêutico , Mycobacterium bovis , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacina BCG/administração & dosagem , Contagem de Linfócito CD4 , Esqueleto da Parede Celular/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
17.
J Microbiol ; 57(9): 821-827, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452045

RESUMO

Most commercialized virus-like particle (VLP) vaccines use aluminum salt as adjuvant, even though VLPs provoke adequate antibody responses without adjuvant. We do not have detailed knowledge of how adjuvant affects the profile of anti-VLP antibodies. Meanwhile, there is evidence that differences between vaccination protocols influence the glycosylation of antibodies, which may alter their effector functions. In the present study a murine model was used to investigate the effects of dosing schedule and adjuvant on the antibody profiles and glycosylation levels of antigen-specific antibody responses to human papillomavirus type 16 L1 (HPV16 L1) VLPs. Mice received subcutaneously 2,000 ng of antigen divided into 4 or 7 doses. The HPV16 L1 VLPs elicited > 4 log10 anti-HPV16 L1 IgG titers without adjuvant, and aluminum hydroxide as adjuvant increased IgG titers 1.3- to 4-fold and reduced the anti-HPV16 L1 IgG2a / anti-HPV16 L1 IgG1 ratio value (use of aluminum hydroxide reduced the ratio of the IgG2a). Immunization with HPV16 L1 VLPs in combination with Freund's adjuvant enhanced IgG titers 5- to 12-fold. Seven-dose immunization markedly increased anti-HPV16 L1 IgM titers compared to four-dose immunization, as well as increasing the proportion of glycosylated antibodies. Our results suggest that antibody glycosylation can be controlled immunologically, and IgG and IgM profiles and glycosylation profiles of the vaccine-induced antibodies can be used as indicators reflecting the vaccine characteristics. These results indicate that the HPV16 L1 VLP dosing schedule can affect the quality of antigen-specific antibody responses. We suggest that dosing schedules should be noted in vaccination protocols for VLP-based vaccines.


Assuntos
Papillomavirus Humano 16/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Papillomavirus Humano 16/genética , Humanos , Esquemas de Imunização , Camundongos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
18.
BMC Infect Dis ; 19(1): 656, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337344

RESUMO

BACKGROUND: The immune response to seasonal influenza vaccines decreases with advancing age. Therefore, an adjuvanted inactivated trivalent influenza vaccine (Fluad®) exists for elderly individuals. Fluad® is more immunogenic and efficacious than conventional influenza vaccines. However, the immune response varies and may still result in high frequencies of poor responders. Therefore, we aimed to a) examine the prevalence of a weak response to Fluad® and b) identify potential risk factors. METHODS: A prospective population-based study among individuals 65-80 years old was conducted in 2015/2016 in Hannover, Germany (n = 200). Hemagglutination-inhibition titers 21 days after vaccination with Fluad® served as indicator of vaccine responsiveness. RESULTS: The percentage of vaccinees with an inadequate vaccine response varied depending on the influenza strain: it was lowest for H3N2 (13.5%; 95% CI, 9.4-18.9%), intermediate for B strain (37.0%; 30.6-43.9%), and highest for H1N1 (49.0%; 42.2-55.9%). The risk of a weak response to the influenza A H1N1 strain was independently associated with self-reported diabetes (AOR, 4.64; 95% CI, 1.16-18.54), a history of herpes zoster (2.27; 1.01-5.10) and, to a much lesser extent, increasing age (change per year, 1.08; 0.99-1.16). In addition, herpes zoster was the only risk factor for a weak response to the H3N2 antigen (AOR, 3.12; 1.18-8.23). We found no significant association between sex, Body Mass Index, cancer, hypertension, heart attack and CMV seropositivity and a weak response to these two influenza A antigens. Despite its occurence in over one third of vaccinees, none of the variables examined proved to be risk factors for a weak response to the B antigen. CONCLUSIONS: A considerable proportion of elderly individuals displayed a weak vaccine response to this adjuvanted seasonal influenza vaccine and further efforts are thus needed to improve immune responses to influenza vaccination among the elderly. Diabetes and herpes zoster were identified as potentially modifiable risk factors for a poor vaccine response against influenza A antigens, but the results also reveal the need for broader investigations to identify risk factors for inadequate responses to influenza B antigens. TRIAL REGISTRATION: No. NCT02362919 (ClinicalTrials.gov, date of registration: 09.02.2015).


Assuntos
Diabetes Mellitus/imunologia , Herpes Zoster/imunologia , Imunidade Humoral , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/farmacologia , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/imunologia , Feminino , Alemanha , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/farmacologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Masculino , Estudos Prospectivos , Estações do Ano , Autorrelato
19.
Mol Plant Microbe Interact ; 32(11): 1475-1486, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31298967

RESUMO

Plant activators, including acibenzolar-S-methyl (ASM), are chemical compounds that stimulate plant defense responses to pathogens. ASM treatment inhibits infection by a variety of plant viruses, however, the mechanisms of this broad-spectrum and strong effect remain poorly understood. We employed green fluorescent protein (GFP)-expressing viruses and Nicotiana benthamiana plants to identify the infection stages that are restricted by ASM. ASM suppressed infection by three viral species, plantago asiatica mosaic virus (PlAMV), potato virus X (PVX), and turnip mosaic virus (TuMV), in inoculated cells. Furthermore, ASM delayed the long-distance movement of PlAMV and PVX, and the cell-to-cell (short range) movement of TuMV. The ASM-mediated delay of long-distance movement of PlAMV was not due to the suppression of viral accumulation in the inoculated leaves, indicating that ASM restricts PlAMV infection in at least two independent steps. We used Arabidopsis thaliana mutants to show that the ASM-mediated restriction of PlAMV infection requires the NPR1 gene but was independent of the dicer-like genes essential for RNA silencing. Furthermore, experiments using protoplasts showed that ASM treatment inhibited PlAMV replication without cell death. Our approach, using GFP-expressing viruses, will be useful for the analysis of mechanisms underlying plant activator-mediated virus restriction.


Assuntos
Potexvirus , Tiadiazóis , Tabaco , Adjuvantes Imunológicos/farmacologia , Resistência à Doença/efeitos dos fármacos , Imunidade Vegetal/efeitos dos fármacos , Potexvirus/fisiologia , Tiadiazóis/farmacologia , Tabaco/imunologia , Tabaco/virologia
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