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1.
Nature ; 602(7896): 307-313, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34937050

RESUMO

Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.


Assuntos
COVID-19/transmissão , COVID-19/virologia , Mutação , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia , Replicação Viral , Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Animais de Laboratório/virologia , COVID-19/veterinária , Cricetinae , Modelos Animais de Doenças , Células Epiteliais/virologia , Feminino , Furões/virologia , Humanos , Masculino , Mesocricetus/virologia , Camundongos , Camundongos Transgênicos , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Virulência/genética
2.
Nature ; 597(7875): 274-278, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33208941

RESUMO

Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood1-8. Here we show that human papillomavirus (HPV)-specific B cell responses are detectable in samples from patients with HPV-positive head and neck cancers, with active production of HPV-specific IgG antibodies in situ. HPV-specific antibody secreting cells (ASCs) were present in the tumour microenvironment, with minimal bystander recruitment of influenza-specific cells, suggesting a localized and antigen-specific ASC response. HPV-specific ASC responses correlated with titres of plasma IgG and were directed against the HPV proteins E2, E6 and E7, with the most dominant response against E2. Using intratumoral B cells and plasma cells, we generated several HPV-specific human monoclonal antibodies, which exhibited a high degree of somatic hypermutation, consistent with chronic antigen exposure. Single-cell RNA sequencing analyses detected activated B cells, germinal centre B cells and ASCs within the tumour microenvironment. Compared with the tumour parenchyma, B cells and ASCs were preferentially localized in the tumour stroma, with well-formed clusters of activated B cells indicating ongoing germinal centre reactions. Overall, we show that antigen-specific activated and germinal centre B cells as well as plasma cells can be found in the tumour microenvironment. Our findings provide a better understanding of humoral immune responses in human cancer and suggest that tumour-infiltrating B cells could be harnessed for the development of therapeutic agents.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Linfócitos do Interstício Tumoral/imunologia , Papillomaviridae/imunologia , Microambiente Tumoral/imunologia , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/genética , Linfócitos B/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/virologia , Separação Celular , Centro Germinativo/citologia , Centro Germinativo/imunologia , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Imunidade Humoral , Imunoglobulina G/sangue , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , RNA-Seq , Análise de Célula Única , Hipermutação Somática de Imunoglobulina/genética , Hipermutação Somática de Imunoglobulina/imunologia , Transcriptoma
3.
Nature ; 597(7875): 279-284, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34471285

RESUMO

T cells are important in tumour immunity but a better understanding is needed of the differentiation of antigen-specific T cells in human cancer1,2. Here we studied CD8 T cells in patients with human papillomavirus (HPV)-positive head and neck cancer and identified several epitopes derived from HPV E2, E5 and E6 proteins that allowed us to analyse virus-specific CD8 T cells using major histocompatibility complex (MHC) class I tetramers. HPV-specific CD8 T cells expressed PD-1 and were detectable in the tumour at levels that ranged from 0.1% to 10% of tumour-infiltrating CD8 T lymphocytes (TILs) for a given epitope. Single-cell RNA-sequencing analyses of tetramer-sorted HPV-specific PD-1+ CD8 TILs revealed three transcriptionally distinct subsets. One subset expressed TCF7 and other genes associated with PD-1+ stem-like CD8 T cells that are critical for maintaining T cell responses in conditions of antigen persistence. The second subset expressed more effector molecules, representing a transitory cell population, and the third subset was characterized by a terminally differentiated gene signature. T cell receptor clonotypes were shared between the three subsets and pseudotime analysis suggested a hypothetical differentiation trajectory from stem-like to transitory to terminally differentiated cells. More notably, HPV-specific PD-1+TCF-1+ stem-like TILs proliferated and differentiated into more effector-like cells after in vitro stimulation with the cognate HPV peptide, whereas the more terminally differentiated cells did not proliferate. The presence of functional HPV-specific PD-1+TCF-1+CD45RO+ stem-like CD8 T cells with proliferative capacity shows that the cellular machinery to respond to PD-1 blockade exists in HPV-positive head and neck cancer, supporting the further investigation of PD-1 targeted therapies in this malignancy. Furthermore, HPV therapeutic vaccination efforts have focused on E6 and E7 proteins; our results suggest that E2 and E5 should also be considered for inclusion as vaccine antigens to elicit tumour-reactive CD8 T cell responses of maximal breadth.


Assuntos
Alphapapillomavirus/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Células-Tronco/citologia , Alphapapillomavirus/isolamento & purificação , Linfócitos T CD8-Positivos/classificação , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Diferenciação Celular , Proliferação de Células , Proteínas de Ligação a DNA/imunologia , Humanos , Linfócitos do Interstício Tumoral/classificação , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/metabolismo , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , RNA-Seq , Receptores de Antígenos de Linfócitos T/imunologia , Análise de Célula Única , Células-Tronco/imunologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Linfócitos T/imunologia , Transcrição Gênica
4.
Pediatr Allergy Immunol ; 35(5): e14161, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38796784

RESUMO

BACKGROUND: Treatment with anti-CD20 antibodies (rituximab) is used in both adults and children to treat various autoimmune and oncological diseases. Rituximab depletes B CD20+ cells and, thereby, antibody response to vaccines. This study aimed to examine the antibody response to mRNA-based COVID-19 vaccines in children aged 5-18 years undergoing rituximab treatment compared to healthy matched children. METHODS: Between 31 January and 18 July 2022, we conducted a prospective observational study at the Geneva University Hospitals, enrolling children aged 5-18 years under rituximab treatment who had received two mRNA-based SARS-CoV-2 vaccine doses. Controls were healthy volunteers with no significant medical conditions. Exclusion criteria included a recent SARS-CoV-2 infection. Blood samples were collected at day 60 (±30) and day 270 (±90) after the second vaccination. RESULTS: The rituximab-treated group exhibited significantly lower levels of antibodies specific to the anti-receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein than healthy controls at 60 (±30) days after the second vaccine dose (geometric mean concentration: 868.3 IU/mL in patients and 11,393 IU/mL in controls; p = .008). However, patients with a rituximab-to-vaccine interval shorter than 6 months and with evidence of a past infection (based on positive anti-N antibody levels) had a high level of anti-RBD antibodies. CONCLUSION: A past infection with SARS-CoV-2 may induce anti-RBD-specific memory B cells that can be re-activated by SARS-CoV-2 vaccination, even after rituximab-induced B-cell depletion. This suggests that it is possible to vaccinate earlier than 6 months after rituximab to develop a good antibody response, especially in the case of past SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Rituximab , SARS-CoV-2 , Humanos , Rituximab/uso terapêutico , Criança , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Feminino , Masculino , Adolescente , Pré-Escolar , Estudos Prospectivos , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina , Glicoproteína da Espícula de Coronavírus/imunologia
5.
Rev Med Suisse ; 20(869): 744-747, 2024 Apr 10.
Artigo em Francês | MEDLINE | ID: mdl-38616685

RESUMO

The number of elderly people is constantly increasing in Switzerland. This population is often at higher risk of infections and concomitant decompensation of underlying comorbidities, in particular cardiac or respiratory diseases. Vaccines are some of the most effective preventive measures for limiting morbidity and mortality related to some of those infections, such as influenza or shingles. In order to improve vaccination coverage, it is essential to inform the patients of the benefits of vaccination, and to plan a catch-up vaccination consultation. The goal of this article is to offer a practical guide for the general practitioner detailing vaccines for the elderly recommended in Switzerland.


Le nombre de personnes âgées est en constante augmentation en Suisse. Celles-ci sont souvent plus à risque de présenter des infections et de façon concomitante une décompensation de leurs comorbidités, notamment cardiaques et respiratoires. La vaccination est l'une des mesures préventives efficaces pour limiter la morbimortalité associée à certaines de ces infections, comme la grippe ou le zona. Afin d'améliorer la couverture vaccinale, il est primordial d'informer les patients sur les bénéfices de la vaccination et de prévoir une consultation dédiée à une mise à jour vaccinale. Le but de cet article est d'offrir un guide pratique pour le médecin de famille sur les différents vaccins recommandés chez la personne âgée.


Assuntos
Clínicos Gerais , Vacinas contra Influenza , Influenza Humana , Idoso , Humanos , Vacinação , Coração , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle
6.
Clin Infect Dis ; 77(4): 645-648, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37073575

RESUMO

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.


Assuntos
Anticorpos Antibacterianos , Coqueluche , Recém-Nascido , Gravidez , Feminino , Humanos , Imunidade Materno-Adquirida , Vacinação , Coqueluche/prevenção & controle , Terceiro Trimestre da Gravidez
7.
Clin Infect Dis ; 75(1): e1037-e1045, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34791081

RESUMO

BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Vacinas Virais , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Estudos Prospectivos , RNA Mensageiro , Rituximab , SARS-CoV-2 , Vacinação
8.
J Hepatol ; 77(4): 1161-1197, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35868584

RESUMO

The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.


Assuntos
COVID-19 , Hepatopatias , Transplante de Fígado , Neoplasias , Humanos , Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Pandemias , SARS-CoV-2
9.
Curr Opin Infect Dis ; 35(4): 312-320, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849521

RESUMO

PURPOSE OF REVIEW: Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance. RECENT FINDINGS: Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations. SUMMARY: Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster , Transplante de Órgãos , Adjuvantes Imunológicos , Idoso , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/efeitos adversos , Herpesvirus Humano 3 , Humanos , Transplante de Órgãos/efeitos adversos , Transplantados , Vacinas Sintéticas/efeitos adversos
10.
Eur J Clin Invest ; 52(10): e13818, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35598178

RESUMO

BACKGROUND: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence. METHODS: All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. RESULTS: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p = 0.03), without affecting the IFN-γ response. CONCLUSION: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.


Assuntos
COVID-19 , Anticorpos Antivirais , Antivirais , Apolipoproteína A-I , Autoanticorpos , Humanos , SARS-CoV-2
11.
Rev Med Suisse ; 18(767): 165-168, 2022 Feb 02.
Artigo em Francês | MEDLINE | ID: mdl-35107890

RESUMO

During this global health crisis, COVID-19 unfortunately did not spare pregnant women, who are at greater risk of becoming infected, developing severe forms and having obstetric complications. In this article we will talk about the risks associated with COVID-19 during pregnancy and in particular the existing data on the drugs to be administered in the event of illness and how to avoid infection and its complications through vaccination.


Durant cette crise sanitaire mondiale, le Covid-19 n'a malheureusement pas épargné les femmes enceintes. Celles-ci sont plus à risque d'être infectées, de développer des formes sévères et d'avoir des complications obstétricales. Dans cet article, nous allons parler des risques liés au Covid-19 durant la grossesse et notamment des données existantes sur les médicaments à administrer en cas de maladie et comment éviter l'infection et ses complications grâce à la vaccination.


Assuntos
COVID-19 , Vacinas contra Influenza , Preparações Farmacêuticas , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2
12.
J Hepatol ; 74(4): 944-951, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33563499

RESUMO

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.


Assuntos
Neoplasias do Sistema Biliar , Vacinas contra COVID-19/farmacologia , COVID-19 , Hepatopatias , Transplante de Fígado , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/terapia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Hepatopatias/epidemiologia , Hepatopatias/imunologia , Hepatopatias/terapia , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Risco Ajustado , SARS-CoV-2 , Vacinação/métodos
13.
J Clin Immunol ; 41(8): 1723-1732, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34581925

RESUMO

BACKGROUND: SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches. METHODS: SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms. RESULTS: Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG. CONCLUSION: The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.


Assuntos
COVID-19/imunologia , Citocinas/biossíntese , Inflamação/etiologia , Mucosa Nasal/imunologia , SARS-CoV-2 , Carga Viral , Adulto , Idoso , Anticorpos Antivirais , COVID-19/virologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/imunologia
14.
Curr Opin Infect Dis ; 34(4): 275-287, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074880

RESUMO

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) vaccination is considered one of the most promising and socioeconomically sustainable strategy to help control the pandemic and several vaccines are currently being distributed in nationwide mass immunization campaigns. Very limited data are available on benefits and risks of COVID-19 vaccination in immunocompromised patients and in particular in solid organ or hematopoietic stem cell transplant recipients as they were excluded from phase III trials. This review summarizes current knowledge, international guidelines and controversies regarding COVID-19 vaccination in these vulnerable populations. RECENT FINDINGS: Various COVID-19 vaccine platforms showed good efficacy in phase III trials in the immunocompetent and there are data arising on the safety and immunogenicity of these vaccines in the immunocompromised population. SUMMARY: Transplant recipients could benefit significantly from COVID-19 vaccination, both through active immunization provided they elicit protective vaccine responses, and probably through cocooning by immunization of caregivers and healthcare personnel and thus reducing the risk of SARS-coronavirus-2 exposure. Although awaiting more data on the safety and efficacy of COVID-19 vaccines to inform potential adaptations of vaccine regimens, we strongly recommend prioritizing COVID-19 vaccination of solid and hematopoietic stem cell transplant recipients to decrease COVID-19-related morbidity and mortality.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Transplantados , COVID-19/etiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/classificação , Tomada de Decisão Clínica , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos , Avaliação de Resultados em Cuidados de Saúde , Vacinação
15.
J Virol ; 94(13)2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32321817

RESUMO

Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.


Assuntos
Vacina contra Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Plasmócitos/imunologia , Anticorpos Antivirais/imunologia , Medula Óssea , Linfócitos T CD4-Positivos/imunologia , Feminino , Herpes Zoster/imunologia , Humanos , Imunidade Celular/imunologia , Interferon gama/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Vacinação , Vacinas Atenuadas/imunologia , Adulto Jovem
16.
Eur J Clin Invest ; 51(11): e13661, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34324704

RESUMO

BACKGROUND: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes. DESIGN: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period. RESULTS: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004). CONCLUSION: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.


Assuntos
Anticorpos Antivirais/imunologia , Apolipoproteína A-I/imunologia , Autoanticorpos/imunologia , COVID-19/imunologia , Citocinas/imunologia , Imunidade Humoral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína A-I/química , Biologia Computacional , Epitopos/química , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Peptídeos , SARS-CoV-2 , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/química , Receptor 2 Toll-Like/química , Receptor 2 Toll-Like/imunologia , Adulto Jovem
17.
Pediatr Allergy Immunol ; 32(1): 9-16, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33113210

RESUMO

Tremendous efforts are undertaken to quickly develop COVID-19 vaccines that protect vulnerable individuals from severe disease and thereby limit the health and socioeconomic impacts of the pandemic. Potential candidates are tested in adult populations, and questions arise of whether COVID-19 vaccination should be implemented in children. Compared to adults, the incidence and disease severity of COVID-19 are low in children, and despite their infectiveness, their role in disease propagation is limited. Therefore, COVID-19 vaccines will need to have fully demonstrated safety and efficacy in preventing not only complications but transmission to justify childhood vaccination. This work summarizes currently tested vaccine platforms and debates practical and ethical considerations for their potential use in children. It also discusses the already deleterious effect of the pandemic on routine childhood vaccine coverage, calling for action to limit the risks for a rise in vaccine-preventable diseases.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Vacinação/métodos , Adolescente , Vacinas contra COVID-19/efeitos adversos , Criança , Pré-Escolar , Humanos , Lactente , Pandemias/prevenção & controle , Fatores de Risco , SARS-CoV-2/imunologia , Vacinação/ética , Vacinas de DNA/uso terapêutico , Vacinas Sintéticas/uso terapêutico , Vacinas de mRNA
18.
Rev Med Suisse ; 17(726): 353-357, 2021 Feb 17.
Artigo em Francês | MEDLINE | ID: mdl-33599412

RESUMO

Considerable efforts have been undertaken to quickly develop COVID-19 vaccines that protect vulnerable adults against severe disease and thus limit the socio-economic and public health impact of the current pandemic. To justify COVID-19 vaccination for the pediatric population, which rarely suffers from severe COVID-19, vaccines will need to have fully demonstrated safety and efficacy in preventing complications and viral transmission. This article summarizes the different vaccine platforms that are currently being tested and discusses practical and ethical aspects of childhood COVID-19 vaccination. It also examines the already deleterious effects of the pandemic on routine childhood vaccine coverage and insists on the imperative to vaccinate all children timely as recommended by national immunization programs.


Des efforts considérables sont entrepris pour développer rapidement des vaccins contre le Covid-19 qui protègent les adultes vulnérables contre ses complications, limitant ainsi les impacts sanitaires et socio-économiques de cette pandémie. Pour justifier une vaccination des enfants, rarement atteints d'un Covid-19 sévère, les vaccins contre cette maladie devront avoir pleinement démontré leur sécurité et leur efficacité dans la prévention des complications et surtout dans la transmission virale. Cet article résume les types de vaccins actuellement testés et discute des aspects pratiques et éthiques d'une vaccination contre le Covid-19 pédiatrique. Il examine également l'effet déjà délétère de la pandémie sur la couverture vaccinale de routine des enfants et insiste sur la nécessité absolue de vacciner tous les enfants sans prendre de retard sur les recommandations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Criança , Humanos , Programas de Imunização , SARS-CoV-2 , Vacinação
19.
Rev Med Suisse ; 17(720-1): 42-49, 2021 Jan 13.
Artigo em Francês | MEDLINE | ID: mdl-33443830

RESUMO

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «â€…PIRATE ¼ indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.


Que dire des nouveautés en maladies infectieuses en 2020 ? L'année a été marquée évidemment par la pandémie du Covid-19, motivant une revue dans cet article, des connaissances actuelles sur le SARS-CoV-2 et de sa prise en charge. Les résultats du projet suisse PIRATE ont montré une non-infériorité pour les bactériémies Gram négatif entre une antibiothérapie de 7 jours ou guidée par la CRP face à une durée de 14 jours. Une étude mongolienne n'a pas permis de montrer le bénéfice d'une substitution en vitamine D chez les enfants sur l'incidence de la tuberculose. Le baloxavir, un nouvel antiviral contre la grippe, a été approuvé par Swissmedic. Et enfin, des nouvelles recommandations américaines sur le monitoring thérapeutique de la vancomycine et sur le dépistage universel de l'hépatite C ont été publiées.


Assuntos
Infectologia/tendências , Antibacterianos/administração & dosagem , Antivirais/uso terapêutico , Proteína C-Reativa/análise , COVID-19 , Criança , Doenças Transmissíveis/tratamento farmacológico , Humanos , Influenza Humana/tratamento farmacológico , Pandemias , Tuberculose/prevenção & controle , Vitamina D/administração & dosagem
20.
Clin Infect Dis ; 69(2): 348-351, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30668661

RESUMO

An immunocompetent adult received corticosteroids for chest pain, which later was clinically found to be herpes zoster (HZ). She developed severe disease and rapid viral dissemination that elicited an exceptionally strong varicella zoster virus-specific B-cell and CD8 T-cell response. Clinicians should consider atypical HZ presentation prior to corticosteroid administration.


Assuntos
Imunidade Adaptativa , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Encefalite por Varicela Zoster/imunologia , Herpesvirus Humano 3/imunologia , Feminino , Humanos , Adulto Jovem
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