Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.250
Filtrar
1.
J Virol ; 98(5): e0169323, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38563763

RESUMO

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform.


Assuntos
Vacinas contra COVID-19 , Vírus do Sarampo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Feminino , Humanos , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Modelos Animais de Doenças , Vetores Genéticos , Vacina contra Sarampo/imunologia , Vacina contra Sarampo/genética , Vírus do Sarampo/imunologia , Vírus do Sarampo/genética , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética
2.
J Virol ; 98(5): e0176223, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38563762

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vírus do Sarampo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Chlorocebus aethiops , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Vírus do Sarampo/imunologia , Vírus do Sarampo/genética , Vacinas contra COVID-19/imunologia , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vetores Genéticos , Células Vero , Pandemias/prevenção & controle , Feminino , Betacoronavirus/imunologia , Betacoronavirus/genética , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Pneumonia Viral/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterinária , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/administração & dosagem , Modelos Animais de Doenças
3.
Emerg Infect Dis ; 30(5): 926-933, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579738

RESUMO

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.


Assuntos
Anticorpos Antivirais , Imunoglobulina M , Vírus do Sarampo , Sarampo , Humanos , Imunoglobulina M/sangue , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/virologia , Sarampo/imunologia , Anticorpos Antivirais/sangue , Japão/epidemiologia , Criança , Pré-Escolar , Vírus do Sarampo/imunologia , Vírus do Sarampo/genética , Masculino , Adulto , Feminino , Lactente , Adolescente , Imunoglobulina G/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Vacina contra Sarampo/imunologia , Adulto Jovem , Reação em Cadeia da Polimerase em Tempo Real/métodos
4.
Immunity ; 43(1): 132-45, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26187412

RESUMO

Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM). We found that the CD19(-)CD38(hi)CD138(+) subset was morphologically distinct, differentially expressed PC-associated genes, and exclusively contained PCs specific for viral antigens to which the subjects had not been exposed for more than 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19(-)CD38(hi)CD138(+) PCs in the BM. Finally, we found that CD19(-)CD38(hi)CD138(+) PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and probably represents the B cell response's "historical record" of antigenic exposure. Thus, our studies define human LLPCs and provide a mechanism for the life-long maintenance of anti-viral antibodies in the serum.


Assuntos
Anticorpos Antivirais/imunologia , Células da Medula Óssea/imunologia , Vírus do Sarampo/imunologia , Vírus da Caxumba/imunologia , Plasmócitos/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Anticorpos Antivirais/sangue , Antígenos CD19/metabolismo , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , Sindecana-1/metabolismo , Adulto Jovem
5.
Eur J Clin Microbiol Infect Dis ; 43(6): 1139-1148, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613705

RESUMO

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.


Assuntos
Anticorpos Antivirais , Varicela , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Medições Luminescentes , Vírus do Sarampo , Sarampo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Sarampo/diagnóstico , Sarampo/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Medições Luminescentes/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Criança , Masculino , Feminino , Adulto , Adolescente , Varicela/diagnóstico , Varicela/imunologia , Vírus do Sarampo/imunologia , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Herpesvirus Humano 3/imunologia , Sensibilidade e Especificidade , Lactente , Idoso , Imunoensaio/métodos , Kit de Reagentes para Diagnóstico/normas
6.
Bull Math Biol ; 86(7): 85, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853189

RESUMO

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.


Assuntos
Macaca fascicularis , Conceitos Matemáticos , Vírus do Sarampo , Sarampo , Carga Viral , Viremia , Sarampo/imunologia , Sarampo/transmissão , Sarampo/prevenção & controle , Sarampo/virologia , Sarampo/epidemiologia , Animais , Viremia/imunologia , Viremia/virologia , Vírus do Sarampo/imunologia , Vírus do Sarampo/patogenicidade , Vírus do Sarampo/fisiologia , Funções Verossimilhança , Humanos , Modelos Imunológicos , Modelos Biológicos , Linfócitos T/imunologia , Ativação Linfocitária
7.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33688034

RESUMO

The current pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters. We found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2-specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent. Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response. The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, body weight loss, cytokine storm, and lung pathology. These data demonstrate that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Vetores Genéticos , Vírus do Sarampo , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/complicações , COVID-19/patologia , Vacinas contra COVID-19/genética , Cricetinae , Modelos Animais de Doenças , Expressão Gênica , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Humanos , Imunização , Imunogenicidade da Vacina , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Camundongos , Camundongos Transgênicos , Ratos , Glicoproteína da Espícula de Coronavírus/genética , Vacinas Sintéticas/genética
8.
Euro Surveill ; 29(22)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38818746

RESUMO

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.


Assuntos
Surtos de Doenças , Vacina contra Sarampo , Vírus do Sarampo , Sarampo , Vacinação , Humanos , Sarampo/prevenção & controle , Sarampo/epidemiologia , Suíça/epidemiologia , Surtos de Doenças/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacinação/estatística & dados numéricos , Masculino , Feminino , Adulto , Adolescente , Criança , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Pré-Escolar , Adulto Jovem , Lactente
9.
Lancet ; 399(10325): 678-690, 2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35093206

RESUMO

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.


Assuntos
COVID-19/epidemiologia , Doenças Endêmicas/prevenção & controle , Vacinação em Massa/organização & administração , Vacina contra Sarampo/administração & dosagem , Sarampo/prevenção & controle , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/organização & administração , Controle de Doenças Transmissíveis/normas , Doenças Endêmicas/estatística & dados numéricos , Humanos , Vacinação em Massa/normas , Vacinação em Massa/estatística & dados numéricos , Sarampo/epidemiologia , Sarampo/imunologia , Sarampo/virologia , Vírus do Sarampo/imunologia , Vírus do Sarampo/patogenicidade , Pandemias/prevenção & controle
10.
Proc Natl Acad Sci U S A ; 117(51): 32657-32666, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33257540

RESUMO

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Vírus do Sarampo/imunologia , SARS-CoV-2/imunologia , Células Th1/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/genética , Humanos , Vacina contra Sarampo/genética , Vacina contra Sarampo/imunologia , Vírus do Sarampo/genética , Camundongos , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia
11.
Mol Cell ; 53(3): 393-406, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24507715

RESUMO

Although thousands of long noncoding RNAs (lncRNAs) are localized in the nucleus, only a few dozen have been functionally characterized. Here we show that nuclear enriched abundant transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, is induced by influenza virus and herpes simplex virus infection as well as by Toll-like receptor3-p38 pathway-triggered poly I:C stimulation, resulting in excess formation of paraspeckles. We found that NEAT1 facilitates the expression of antiviral genes including cytokines such as interleukin-8 (IL8). We found that splicing factor proline/glutamine-rich (SFPQ), a NEAT1-binding paraspeckle protein, is a repressor of IL8 transcription, and that NEAT1 induction relocates SFPQ from the IL8 promoter to the paraspeckles, leading to transcriptional activation of IL8. Together, our data show that NEAT1 plays an important role in the innate immune response through the transcriptional regulation of antiviral genes by the stimulus-responsive cooperative action of NEAT1 and SFPQ.


Assuntos
Imunidade Inata/genética , Interleucina-8/genética , RNA Longo não Codificante/fisiologia , Proteínas de Ligação a RNA/metabolismo , Regulação da Expressão Gênica , Células HeLa , Herpesvirus Humano 1/imunologia , Humanos , Vírus do Sarampo/imunologia , Orthomyxoviridae/imunologia , Fator de Processamento Associado a PTB , Regiões Promotoras Genéticas , Transporte Proteico , RNA Longo não Codificante/genética , Transcrição Gênica
12.
Biologicals ; 79: 19-26, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36096853

RESUMO

Canine morbillivirus is a highly contagious multi-host pathogen with high morbidity and mortality. Timely diagnosis is of utmost importance to effectively control such a dreadful disease. Monoclonal antibodies (mAbs) serve as a high throughput diagnostics and applied tools for research and development (R&D). In the present study, a total of six mouse monoclonal antibodies were developed. All the mAbs generated belonged to IgG class. Of the six mAbs, two of them, namely CD-2F8 and CD-3D8 were directed against the nucleocapsid protein of CDV as determined in western blotting. The reactivity of all the mAbs was checked in indirect-ELISA and cell-ELISA using different morbilliviruses. The mAbs could broadly be categorized as; CDV specific (CD-3D8 and CD-2F8), cross-reactive to PPR virus (CD-AB3 and CD-4D6) and cross-reactive to both PPR virus and measles virus (CD-5D10 and CD-6E5). The characterized mAbs were used for antigenic profiling of CDV, PPR virus and measles virus. Based on the reactivity pattern; a close antigenic relationship was found among CDV and PPR virus as compared to measles virus. A pair of CDV specific mAbs namely CD-2F8 and CD-3D8 were identified which did not cross-react with measles and PPR viruses and thus could be used for diagnostic applications.


Assuntos
Anticorpos Monoclonais , Vírus da Cinomose Canina , Animais , Anticorpos Monoclonais/química , Vírus da Cinomose Canina/imunologia , Cães , Imunoglobulina G , Vírus do Sarampo/imunologia , Camundongos , Proteínas do Nucleocapsídeo , Vírus da Peste dos Pequenos Ruminantes/imunologia
13.
J Infect Dis ; 224(12 Suppl 2): S420-S428, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590128

RESUMO

The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles.


Assuntos
Erradicação de Doenças , Saúde Global , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/imunologia , Sarampo/prevenção & controle , Erradicação de Doenças/tendências , Humanos , Programas de Imunização , Incidência , Lactente , Sarampo/epidemiologia , Vírus do Sarampo/isolamento & purificação , Vigilância da População , Organização Mundial da Saúde
14.
J Infect Dis ; 224(6): 1015-1023, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-33528506

RESUMO

In 2019, the United States (US) experienced the highest number of measles importations and cases in the postelimination era. More than a quarter of imported cases entered the US through California. Measles surveillance efforts in California resulted in the identification of 26 importations, 6 outbreaks, and 72 cases in 2019. Only genotype B3 and D8 measles strains were detected. Genotype-specific differences were noted in the incidence of vaccine failures, hospitalizations, and severe complications among cases. A targeted whole genome sequencing approach provided higher-resolution discrimination between epidemiologically linked and sporadically introduced strains than conventional N450 sequencing. Our report underscores the importance of ensuring appropriate measles vaccination status, especially prior to international travel to measles-endemic regions, and highlights the value of a strong measles surveillance system in minimizing outbreaks and preserving measles elimination status in the US.


Assuntos
Surtos de Doenças , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo , Sarampo/epidemiologia , Adolescente , Adulto , Idoso , California/epidemiologia , Criança , RNA Polimerases Dirigidas por DNA , Feminino , Genótipo , Humanos , Masculino , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Análise de Sequência de DNA , Estados Unidos/epidemiologia , Adulto Jovem
15.
J Med Virol ; 93(6): 3446-3454, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33325052

RESUMO

Since the elimination of the measles virus, patients with vaccination records for the measles-containing vaccine have increased in Japan. According to several studies, the transmission risk from previously immunized patients, especially those with secondary vaccine failure (SVF), is lower than that from those with primary measles infections. Immunological features of SVF were identified per specific immunoglobulin G (IgG) induction with high avidity and high plaque reduction neutralization antibody concentration. However, the virological features of SVF have not been well investigated. To examine not only immunological but also virological differences between SVF and immunologically naive patients, throat swabs and blood and urine specimens of 25 patients with confirmed measles infection after an outbreak at the Kansai International Airport in 2016 were analyzed. Patients were categorized as naive (n = 3) or with SVF (n = 22) based on measles-specific IgG antibody concentrations and their avidity. Virus isolation and quantitative real-time polymerase chain reaction were performed to quantify the viral load in clinical specimens and estimate the infectivity in each specimen. The number of viral genome copies in the blood specimens of those with SVF was significantly different and approximately 1 out of 100 of that in immunologically naive patients. However, genome copy numbers in throat swabs and urine specimens were not significantly different between the groups. The virus was isolated only from those in the naive group. Our study indicated low transmission risk of the virus in patients with SVF.


Assuntos
Aeroportos , Anticorpos Antivirais/sangue , Surtos de Doenças/estatística & dados numéricos , Vacina contra Sarampo/imunologia , Sarampo/epidemiologia , Sarampo/transmissão , Adulto , Anticorpos Neutralizantes/sangue , Feminino , Genoma Viral , Humanos , Imunização Secundária/estatística & dados numéricos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Japão , Masculino , Sarampo/sangue , Sarampo/imunologia , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Vacinação , Carga Viral , Adulto Jovem
16.
J Med Virol ; 93(8): 5141-5145, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33527448

RESUMO

The increase of the evolutionary pressure will cause phylodynamics changes of viruses. In post-vaccine coverage era, measles viruses face more immune pressure than ever before. Vice versa, the phylodynamic changes may reflect herd immunity level provided by vaccination. In this study, we analyzed phylodynamic characteristics of measles viruses isolated from 2005 to 2017 in Jiangsu province of China using nucleoprotein gene sequences of measles viruses. The phylogenetic tree was constructed with Markov chain Monte Carlo algorithm. The mean gene distance within each group was computed with MEGA7.0 software. Our results showed that a decline trend is observed in the gene distance of nucleoprotein gene with time as well as incidence of measles from epidemic surveillance system. Two clusters of H1a genotype show cocirculation of multiple variants in early years and the disappearance of most variants with time. We explore the phylodynamic of measles virus under high immune pressure. Our findings highlight that phylodynamic of measles viruses is a helpful tool to assess the effectiveness of epidemic control.


Assuntos
Vacina contra Sarampo/imunologia , Vírus do Sarampo/genética , Sarampo/epidemiologia , Sarampo/virologia , China/epidemiologia , Genótipo , Humanos , Incidência , Sarampo/prevenção & controle , Vírus do Sarampo/classificação , Vírus do Sarampo/imunologia , Epidemiologia Molecular , Proteínas do Nucleocapsídeo/genética , Filogenia
17.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34375002

RESUMO

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Assuntos
Imunidade Inata , Moléculas com Motivos Associados a Patógenos/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Proteínas Virais/metabolismo , Viroses/imunologia , Vírus/imunologia , Animais , HIV/imunologia , HIV/metabolismo , HIV/patogenicidade , Hepacivirus/imunologia , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Herpesviridae/imunologia , Herpesviridae/metabolismo , Herpesviridae/patogenicidade , Humanos , Vírus do Sarampo/imunologia , Vírus do Sarampo/metabolismo , Vírus do Sarampo/patogenicidade , Moléculas com Motivos Associados a Patógenos/química , Vírus Sinciciais Respiratórios/imunologia , Vírus Sinciciais Respiratórios/metabolismo , Vírus Sinciciais Respiratórios/patogenicidade , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Proteínas Virais/química , Viroses/virologia , Vírus/metabolismo , Vírus/patogenicidade
18.
Microbiol Immunol ; 65(7): 265-272, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33951212

RESUMO

This study investigated the correlation between biochemical markers and viral load among 38 measles cases, including 15 immunologically naive patients and 23 patients with secondary vaccine failure (SVF). We examined four biochemical markers, namely, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and lactate dehydrogenase (LDH) and their relationship between virus genome copy numbers in peripheral blood mononuclear cells (PBMCs) and throat swabs as well as the concentration of measles-specific IgG. Although viral genome copies in both clinical specimens showed a significant correlation with specific IgG concentration, they had a higher correlation in PBMCs (Pearson's product-moment correlation coefficient, -0.662; p < .0001) than in throat swabs (Spearman's rank correlation coefficient, -0.443; p = .0078). The viral load in PBMCs also significantly correlated with LDH values (correlation coefficient, 0.360; p = .036). Thus, the serum LDH level might be a potential auxiliary indicator to distinguish immunologically naive patients with measles from those with SVF.


Assuntos
Sarampo , Anticorpos Antivirais , Biomarcadores , Humanos , Imunoglobulina G , L-Lactato Desidrogenase , Leucócitos Mononucleares , Vacina contra Sarampo , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Carga Viral
20.
Allergol Immunopathol (Madr) ; 49(3): 193-201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938206

RESUMO

BACKGROUND: Measles vaccinations have been suggested to provide immune protection and decreased measles incidence. However, there was a limited study evaluating how the measles vaccine elicits specific immune responses. OBJECTIVE: This study aimed to evaluate both humoral and cellular immunity to first-dose measles vaccine Edmonston-Zagreb (EZ) in 9-month-old Indonesian infants. METHODS: A cohort study was conducted on 9-month-old infants who got the first-dose of measles vaccine EZ. Measles-specific immunoglobulin G (IgG) antibody serum levels were measured using plaque-reduction microneutralization assay. Peripheral blood mononuclear cells were stimulated with a measles-specific peptide to identify a cellular immune response. Quantification of CD4+ and CD8+ T-cells producing interferon-gamma (IFN-É£) and interleukin 17-A (IL-17A) were conducted by flow cytometry. Humoral and cellular immune response parameters were analyzed over time. RESULTS: The prevalence of seropositivity rates was 85.8% at 1-month after vaccination and 16.67% at 6-months postvaccination. Measles-specific IgG antibodies increased significantly at 1-month after measles vaccination. However, they decreased significantly 6-months after vaccination. IFN-É£ and IL-17A secreting T-cells increased significantly at 1-month after measles vaccination. Interestingly, a significant decrease of IFN-É£ and IL-17A secreting CD4+ T cells was noticed 6-months postvaccination compared to IFN-É£ and IL-17A secreting CD8+ T cells. CONCLUSION: Our study suggests that the first-dose measles vaccine on 9-months-old infants seems to induce both humoral and cellular immune responses that decline 6-months after vaccination.


Assuntos
Especificidade de Anticorpos , Imunidade Celular , Vacina contra Sarampo/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Indonésia , Lactente , Interferon gama/metabolismo , Interleucina-17/metabolismo , Leucócitos Mononucleares/imunologia , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA