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1.
Clin Epigenetics ; 16(1): 68, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773655

RESUMO

BACKGROUND: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL. RESULTS: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ ß ≤ 0.8) with large intertumor variation and overall low hypermethylation (ß > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (ß < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499-31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286-18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239-21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319-27.397) and PFS (HR 4.689, 95% CI 1.102-19.963) in LBCL treated with R-CHOP-like regimens. CONCLUSION: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.


Assuntos
Metilação de DNA , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Metilação de DNA/genética , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Adulto , Rituximab/uso terapêutico , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Telômero/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encurtamento do Telômero/genética , Epigênese Genética/genética , Ilhas de CpG/genética
2.
Thromb Res ; 233: 41-54, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38006765

RESUMO

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.


Assuntos
Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Virus Puumala , Trombocitopenia , Humanos , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/terapia , Células Endoteliais
3.
Cancer Immunol Res ; 11(1): 72-92, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36478037

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by rich deposits of extracellular matrix (ECM), affecting the pathophysiology of the disease. Here, we identified galectin 4 (gal 4) as a cancer cell-produced protein that was deposited into the ECM of PDAC tumors and detected high-circulating levels of gal 4 in patients with PDAC. In orthotopic transplantation experiments, we observed increased infiltration of T cells and prolonged survival in immunocompetent mice transplanted with cancer cells with reduced expression of gal 4. Increased survival was not observed in immunodeficient RAG1-/- mice, demonstrating that the effect was mediated by the adaptive immune system. By performing single-cell RNA-sequencing, we found that the myeloid compartment and cancer-associated fibroblast (CAF) subtypes were altered in the transplanted tumors. Reduced gal 4 expression associated with a higher proportion of myofibroblastic CAFs and reduced numbers of inflammatory CAFs. We also found higher proportions of M1 macrophages, T cells, and antigen-presenting dendritic cells in tumors with reduced gal 4 expression. Using a coculture system, we observed that extracellular gal 4 induced apoptosis in T cells by binding N-glycosylation residues on CD3ε/δ. Hence, we show that gal 4 is involved in immune evasion and identify gal 4 as a promising drug target for overcoming immunosuppression in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Galectina 4 , Evasão da Resposta Imune , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Apoptose , Neoplasias Pancreáticas
4.
Sci Immunol ; 7(73): eabq3511, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35549299

RESUMO

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses after Omicron/BA.1 infection in messenger RNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.


Assuntos
Linfócitos B , COVID-19 , Memória Imunológica , Anticorpos Antivirais , Linfócitos B/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Reações Cruzadas , Humanos , Glicoproteínas de Membrana , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral
5.
Infect Dis (Lond) ; 54(4): 283-291, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34878955

RESUMO

BACKGROUND: Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. METHODS: We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). RESULTS: In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. CONCLUSION: As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.


Assuntos
COVID-19 , Imunização Passiva , Hospedeiro Imunocomprometido , COVID-19/terapia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Suécia , Soroterapia para COVID-19
6.
Sci Rep ; 9(1): 4276, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862884

RESUMO

A majority of lymphomas are derived from B cells and novel treatments are required to treat refractory disease. Neurotransmitters such as serotonin and dopamine influence activation of B cells and the effects of a selective serotonin 1A receptor (5HT1A) antagonist on growth of a number of B cell-derived lymphoma cell lines were investigated. We confirmed the expression of 5HT1A in human lymphoma tissue and in several well-defined experimental cell lines. We discovered that the pharmacological inhibition of 5HT1A led to the reduced proliferation of B cell-derived lymphoma cell lines together with DNA damage, ROS-independent caspase activation and apoptosis in a large fraction of cells. Residual live cells were found 'locked' in a non-proliferative state in which a selective transcriptional and translational shutdown of genes important for cell proliferation and metabolism occurred (e.g., AKT, GSK-3ß, cMYC and p53). Strikingly, inhibition of 5HT1A regulated mitochondrial activity through a rapid reduction of mitochondrial membrane potential and reducing dehydrogenase activity. Collectively, our data suggest 5HT1A antagonism as a novel adjuvant to established cancer treatment regimens to further inhibit lymphoma growth.


Assuntos
Autofagia/fisiologia , Linfoma de Células B/metabolismo , Receptores de Serotonina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Apoptose/fisiologia , Autofagia/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Dano ao DNA/genética , Dano ao DNA/fisiologia , Humanos , Linfoma de Células B/genética , Potencial da Membrana Mitocondrial , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Serotonina/genética , Receptores 5-HT1 de Serotonina/genética , Receptores 5-HT1 de Serotonina/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Adulto Jovem
7.
J Immunol ; 191(1): 44-51, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23740950

RESUMO

Abs that bind the functional envelope glycoprotein (Env) spike are considered critical for a broadly effective prophylactic HIV-1 vaccine. The difficulty in eliciting such Abs by vaccination is partially attributed to the immunodominance of hydrophilic, surface-exposed variable protein regions of Env. However, little is known about the potential for competition between B cells that recognize distinct and distal epitopes on Env during protein subunit vaccination. In this study, we address this basic question at the level of Ab-secreting cells and serum IgG using a pair of isogenic soluble Env trimers, designated wildtype and gV3, which differ only in their potential to activate B cell responses against the highly immunogenic V3 region of Env. Immunization of mice with gV3 resulted in a markedly lower Ag-specific response compared with that induced by wildtype Env and could be explained by a loss of V3-directed reactivities. There was no redistribution of the response to other regions of Env in gV3-inoculated mice, suggesting that the epitope-specific Ab-secreting cell responses measured after boost are independently regulated rather than dictated by direct or indirect competition between B cells recognizing different structural elements of Env. This information is relevant for ongoing efforts in Env immunogen design to focus responses on conserved neutralizing determinants and for our general understanding of B cell responses to large-protein Ags that display numerous B cell epitopes.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Diferenciação Celular/imunologia , Epitopos de Linfócito B/biossíntese , Epitopos de Linfócito B/imunologia , Vacinas contra a AIDS/química , Vacinas contra a AIDS/imunologia , Animais , Subpopulações de Linfócitos B/citologia , Epitopos de Linfócito B/metabolismo , Feminino , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunização Secundária , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasmócitos/citologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , Subunidades Proteicas/administração & dosagem , Subunidades Proteicas/química , Subunidades Proteicas/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
8.
J Infect Dis ; 207(3): 426-31, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23162135

RESUMO

The envelope glycoproteins (Env) represent a critical component of a successful antibody-mediated human immunodeficiency virus type 1 (HIV-1) vaccine. However, immunization with soluble Env was reported to induce short-lived antibody responses, suggesting that Env has unusual immunogenic properties. Here, we directly compared the magnitude and durability of B-cell responses induced by HIV-1 Env and an unrelated soluble viral protein, influenza virus hemagglutinin (HA), in simultaneously inoculated macaques. We demonstrate robust peak responses followed by rapid contraction of circulating antibody and memory B cells for both antigens, suggesting that short-lived responses are not unique to HIV-1 Env but may be a common feature of soluble protein vaccines.


Assuntos
Linfócitos B/imunologia , HIV-1/imunologia , Imunização , Orthomyxoviridae/imunologia , Proteínas do Envelope Viral/imunologia , Vacinas contra a AIDS/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Feminino , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Imunidade Humoral , Imunização Secundária , Vacinas contra Influenza/imunologia , Macaca/imunologia , Proteínas Recombinantes/imunologia
9.
J Immunol ; 183(5): 3373-82, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19696434

RESUMO

The HIV-1 envelope glycoprotein (Env) functional spike has evolved multiple immune evasion strategies, and only a few broadly neutralizing determinants on the assembled spike are accessible to Abs. Serological studies, based upon Ab binding and neutralization activity in vitro, suggest that vaccination with current Env-based immunogens predominantly elicits Abs that bind nonneutralizing or strain-restricted neutralizing epitopes. However, the fractional specificities of the polyclonal mixture of Abs present in serum, especially those directed to conformational Env epitopes, are often difficult to determine. Furthermore, serological analyses do not provide information regarding how repeated Ag inoculation impacts the expansion and maintenance of Env-specific B cell subpopulations. Therefore, we developed a highly sensitive Env-specific B cell ELISPOT system, which allows the enumeration of Ab-secreting cells (ASC) from diverse anatomical compartments directed against different structural determinants of Env. In this study, we use this system to examine the evolution of B cell responses in mice immunized with engineered Env trimers in adjuvant. We demonstrate that the relative proportion of ASC specific for defined structural elements of Env is altered significantly by homologous booster immunizations. This results in the selective expansion of ASC directed against the variable regions of Env. We suggest that the B cell specificity and compartment analysis described in this study are important complements to serological mapping studies for the examination of B cell responses against subspecificities of a variety of immunogens.


Assuntos
Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/virologia , Epitopos de Linfócito B/imunologia , Memória Imunológica , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Células Produtoras de Anticorpos/imunologia , Células Produtoras de Anticorpos/metabolismo , Células Produtoras de Anticorpos/virologia , Subpopulações de Linfócitos B/metabolismo , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/virologia , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito B/administração & dosagem , Anticorpos Anti-HIV/biossíntese , Anticorpos Anti-HIV/sangue , Memória Imunológica/genética , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Baço/citologia , Baço/imunologia , Baço/virologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/biossíntese , Produtos do Gene env do Vírus da Imunodeficiência Humana/química
10.
J Gen Virol ; 89(Pt 12): 2954-2964, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19008380

RESUMO

Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env.


Assuntos
Vacinas contra a AIDS , Adjuvantes Imunológicos/administração & dosagem , Toxina da Cólera , Produtos do Gene env/imunologia , HIV-1/imunologia , Proteínas Recombinantes de Fusão , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Administração Intranasal , Animais , Toxina da Cólera/administração & dosagem , Toxina da Cólera/imunologia , Feminino , Produtos do Gene env/administração & dosagem , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Humanos , Imunização , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/imunologia
11.
J Gen Virol ; 88(Pt 10): 2774-2779, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17872531

RESUMO

Viral vectors encoding heterologous vaccine antigens are potent inducers of cellular immune responses, but they are generally less efficient at stimulating humoral immunity. To improve the induction of antibody responses by Semliki Forest virus-based vaccines, a vector encoding a translation-enhancer element and a novel internal signal sequence for increased expression and secretion of soluble antigens was designed. Approximately tenfold more human immunodeficiency virus type 1 gp120 was secreted into culture supernatants of infected cells using the enhanced vector compared with the parental vector. This translated into a significant increase in gp120-specific antibodies in immunized mice, suggesting that antigen-expression levels from the parental vector are limiting for induction of antibody responses. These data encourage the use of the enhanced vector for elicitation of immune responses against heterologous antigens during vaccination.


Assuntos
Anticorpos Anti-HIV/biossíntese , HIV-1/genética , Vírus da Floresta de Semliki/genética , Proteínas do Envelope Viral/genética , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Cricetinae , Regulação Viral da Expressão Gênica , Vetores Genéticos , Proteína gp120 do Envelope de HIV/biossíntese , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Rim , Metionina/metabolismo , Fragmentos de Peptídeos/química , Vírus da Floresta de Semliki/imunologia , Proteínas do Envelope Viral/biossíntese
12.
J Virol ; 79(17): 10902-14, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16103142

RESUMO

The current lack of envelope glycoprotein immunogens that elicit broadly neutralizing antibody responses remains a major challenge for human immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent design and construction of stable soluble gp140 trimers have shown that some neutralization breadth can be achieved by using immunogens that better mimic the functional viral spike complex. The use of genetic delivery systems to drive the in vivo expression of such immunogens for the stimulation of neutralizing antibodies against HIV-1 may offer advantages by maintaining the quaternary structure of the trimeric envelope glycoproteins. Here, we describe the biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein trimers expressed by recombinant Semliki Forest virus (rSFV). The results presented here demonstrate that rSFV supports the expression of stable soluble gp140 trimers that retain recognition by conformationally sensitive antibodies. Further, we show that rSFV particle immunizations efficiently primed immune responses as measured after a single boost with purified trimeric gp140 protein, resulting in a Th1-biased antibody response. This differed from the Th2-biased antibody response obtained after repeated immunizations with purified gp140 protein trimers. Despite this difference, both regimens stimulated neutralizing antibody responses of similar potency. This suggests that rSFV may be a useful component of a viral vector prime-protein boost regimen aimed at stimulating both cell-mediated immune responses and neutralizing antibodies against HIV-1.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/metabolismo , Produtos do Gene env/imunologia , Produtos do Gene env/metabolismo , Infecções por HIV/imunologia , Imunização , Vírus da Floresta de Semliki/metabolismo , Vacinas contra a AIDS/química , Animais , Células Cultivadas , Feminino , Produtos do Gene env/química , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Esquemas de Imunização , Contagem de Linfócitos , Camundongos , Testes de Neutralização , Coelhos , Vírus da Floresta de Semliki/genética , Solubilidade , Baço/imunologia , Células Th1/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana
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