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1.
BMC Infect Dis ; 20(1): 753, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054715

RESUMO

BACKGROUND: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. CASE PRESENTATION: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae. CONCLUSION: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.


Assuntos
Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo-Caxumba-Rubéola/uso terapêutico , Sarampo/etiologia , Natalizumab/uso terapêutico , Adulto , Exantema/induzido quimicamente , Feminino , Febre/etiologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Sarampo/diagnóstico , Vacina contra Sarampo/uso terapêutico , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico
3.
Biomolecules ; 10(10)2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066343

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic spreading around the world, causing massive distress to the world's economy and affecting healthcare systems worldwide. Although some exposed individuals have no symptoms and most symptomatic infections are not severe, COVID-19 cases span a wide spectrum, ranging from mild to critical and sometimes resulting in life-threatening complications, such as pneumonia, severe respiratory distress and cardiac problems. Currently, there is no curative drug for COVID-19 and vaccines are still under development. We are presenting here a strategy for the fast development of natural live-attenuated SARS-CoV-2 vaccines. Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness.


Assuntos
Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos
4.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
5.
J Immunol Res ; 2020: 2837670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964056

RESUMO

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides "RIRGGDGKMKDL" and "AFGRRGPEQTQGNFG" were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteínas do Nucleocapsídeo/imunologia , Nucleocapsídeo/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas do Nucleocapsídeo/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/imunologia , Motivos de Ligação ao RNA/imunologia , Receptor 5 Toll-Like/metabolismo , Vacinas Atenuadas/imunologia , Vacinas de Subunidades/imunologia
6.
Arch Virol ; 165(12): 2777-2788, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32964293

RESUMO

Besides the vaccine strains, the Malaysian variant (MV) and QX-like are the predominant IBVs detected on commercial poultry farms. These two virus strains are distinct based on genomic and pathogenicity studies. In this study, we determined the sequence of the S1 gene and compared the pathogenicity of serial passage 70 (P70) of Malaysian QX-like (QX/P70) and MV (MV/P70) strains with that of their respective wild-type viruses. The nucleotide and amino acid sequences of the complete S1 genes of QX/P70 and MV/P70 showed 1.4 to 1.6% and 3.0 to 3.3% variation, respectively, when compared to the wild-type virus. Most of the mutations were insertions and substitutions in the hypervariable regions (HVRs), primarily in HVR 3. Furthermore, selection pressure analysis showed that both viruses are under purifying selection. A pathogenicity study in specific-pathogen-free (SPF) chickens showed a reduction in respiratory and kidney lesions in chickens inoculated with MV/P70, but not with QX/P70, when compared to the respective wild-type viruses. However, MV/P70 is still pathogenic and can cause ciliary damage. In conclusion, the MV IBV strain is more responsive than the QX-like IBV strain following the attenuation process used for the development of a live attenuated IBV vaccine.


Assuntos
Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/genética , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia , Animais , Galinhas , Infecções por Coronavirus/virologia , Vírus da Bronquite Infecciosa/patogenicidade , Doenças das Aves Domésticas/prevenção & controle , Análise de Sequência de Proteína , Inoculações Seriadas , Organismos Livres de Patógenos Específicos , Vacinas Atenuadas/imunologia
7.
Curr Opin HIV AIDS ; 15(6): 351-358, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969973

RESUMO

PURPOSE OF REVIEW: Coronavirus disease-19 (COVID-19) is a highly transmittable and pathogenic pneumonia-causing disease, which is caused by severe acute respiratory syndrome coronavirus-2, resulting in millions of deaths globally. Severe acute respiratory syndrome coronavirus-2 may coexist with human populations for a long time. Therefore, high-effective COVID-19 vaccines are an urgent need. RECENT FINDINGS: Vaccines help in the development of long-lasting humoral or cellular immunity, or both, by exposing individuals to antigens that induce an immunological response and memory prior to infections with live pathogens. New vaccine technologies, such as viral vectors and nucleic acid-based vaccines, which represent highly versatile technologies, may allow for faster vaccine manufacture and scale up production. SUMMARY: We summarized the recent progress made in relation to COVID-19 vaccine development using several promising technologies, with particular emphasis on advancements that are currently at the clinical trial stage.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Adenoviridae/genética , Infecções por Coronavirus/imunologia , Humanos , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia
8.
Poult Sci ; 99(9): 4351-4359, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867979

RESUMO

The vaccines currently available to control infectious bursal disease (IBD) include live-attenuated and inactivated vaccines, immune-complex vaccines, and vaccines consisting of viral constructs of herpesvirus of turkeys genetically engineered to express VP2 surface protein. To evaluate the impact of vaccines on the chicken immune system, 2 animal trials were performed in specific pathogen-free broiler chickens. In trial 1, birds were either vaccinated when they are one-day old with a dual recombinant herpes virus of turkey construct vaccine, expressing VP2 protein of (IBDV) and F protein of Newcastle disease virus, or an immune-complex IBDV vaccine or birds were not vaccinated. At 14, 28, and 35 D, the bursa of Fabricius was collected for bursa:body weight (B:BW) ratio calculation. In trial 2, birds were vaccinated when they were 1-day old according to the same protocol as trial 1, but at day 14, all groups also received a live infectious bronchitis (IB) vaccine. At 0, 7, 14, 21, and 28 days after IB vaccination, birds were tested by ELISA for IB serology and, soon after the last blood sampling, they were euthanized for collection of Harderian glands, trachea, and spleen and testing by flow cytometry for characterization of mononuclear cells. The immune-complex vaccine groups showed significantly lower B:BW ratio, lower IBV antibody titers, and higher mean percentage of CD8+ T cells in the spleen, trachea, and Harderian glands than those in the other experimental groups. The results of the in vivo trials coupled with a depth analysis of the repertoire of parameters involved in the immune response to IBD and IB vaccinations show one vaccine may influence the immune response of other vaccines included in the vaccination program.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças das Aves Domésticas/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Birnaviridae/imunologia , Bolsa de Fabricius/patologia , Galinhas , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Vacinação/veterinária , Vacinas Atenuadas/imunologia
9.
Arch Virol ; 165(11): 2675-2677, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32772251

RESUMO

An uncharacteristic outbreak of lumpy skin disease was reported in the Republic of Udmurtiya, Russia, during the climatic winter of March 2019. The causative lumpy skin disease virus (LSDV_Udmurtiya_Russia_2019) was shown to be a recombinant composed of a live attenuated Neethling-type vaccine strain as the dominant parental strain and a Kenyan KSGP/NI-2490-like virus as its minor parental strain, with 24 statistically significant recombination events that are not identical to those in LSDV Saratov/2017, in which 27 events were identified.


Assuntos
Surtos de Doenças/veterinária , Doença Nodular Cutânea/epidemiologia , Vírus da Doença Nodular Cutânea/isolamento & purificação , Animais , Bovinos , DNA Viral/genética , Vírus da Doença Nodular Cutânea/genética , Reação em Cadeia da Polimerase , Federação Russa/epidemiologia , Estações do Ano , Vacinação/veterinária , Vacinas Atenuadas/imunologia
10.
PLoS Pathog ; 16(8): e1008703, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776994

RESUMO

Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in the UL7, UL41, LAT, Us3, Us11 and Us12 genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.


Assuntos
Vacinas contra o Vírus do Herpes Simples/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Animais , Feminino , Herpes Simples/prevenção & controle , Herpes Simples/virologia , Vacinas contra o Vírus do Herpes Simples/administração & dosagem , Vacinas contra o Vírus do Herpes Simples/genética , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Fenótipo , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Proteínas Virais/imunologia
11.
Front Immunol ; 11: 1959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849655

RESUMO

The lung is the vital target organ of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the majority of patients the most active virus replication seems to be found in the upper respiratory tract, severe cases however suffer from SARS-like disease associated with virus replication in lung tissues. Due to the current lack of suitable anti-viral drugs the induction of protective immunity such as neutralizing antibodies in the lung is the key aim of the only alternative approach-the development and application of SARS-CoV-2 vaccines. However, past experience from experimental animals, livestock, and humans showed that induction of immunity in the lung is limited following application of vaccines at peripheral sides such as skin or muscles. Based on several considerations we therefore propose here to consider the application of a Modified Vaccinia virus Ankara (MVA)-based vaccine to mucosal surfaces of the respiratory tract as a favorable approach to combat COVID-19.


Assuntos
Betacoronavirus/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus Vaccinia/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Administração através da Mucosa , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Brônquios/imunologia , Infecções por Coronavirus/virologia , Humanos , Imunoglobulina A/metabolismo , Tecido Linfoide/imunologia , Plasmócitos/imunologia , Pneumonia Viral/virologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Linfócitos T/imunologia , Vacinação , Vacinas Atenuadas/imunologia
12.
J Immunol ; 205(8): 1990-1997, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32826281

RESUMO

The recent outbreak of COVID-19 has emerged as a major global health concern. Although susceptible to infection, recent evidence indicates mostly asymptomatic or mild presentation of the disease in infants, children, and adolescents. Similar observations were made for acute respiratory infections caused by other coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome). These observations suggest that the immune system behaves differently in children than adults. Recent developments in the field demonstrated fundamental differences in the neonatal immune system as compared with adults, whereby infants respond to microorganisms through biased immune tolerance rather than resistance strategies. Similarly, more frequent/recent vaccinations in children and younger populations may result in trained immunity. Therefore, the physiological abundance of certain immunosuppressive cells, a tightly regulated immune system, and/or exposure to attenuated vaccines may enhance trained immunity to limit excessive immune reaction to COVID-19 in the young.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Sistema Imunitário/imunologia , Tolerância Imunológica , Pneumonia Viral/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Suscetibilidade a Doenças , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Internalização do Vírus
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(7): 1138-1144, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32741184

RESUMO

Objective: To assess the effectiveness of 1 dose varicella attenuated live vaccine (VarV) for healthy children aged 1-12 years in China and explore the application of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework in observational studies of vaccine effectiveness (VE). Methods: We searched studies about the VE of 1-dose VarV for children aged 1-12 years in China which published before 2019 and evaluated the quality of the studies by the Newcastle Ottawa Scale (NOS) table. We used Meta-analysis models to obtain the pooled 1-dose VE and that in subgroups by study design, outbreak or not, study quality and age of subjects. The evidences of VEs were rated by means of the GRADE system. Results: Thirty-two studies were included and the pooled 1-dose VE was 75% [95% confidence interval (CI): 68%-80%]. The VE of outbreak studies [VE=66% (95%CI: 57%-73%)] was lower than non-outbreak studies [VE=85% (95%CI: 78%-89%)], and the VE in <6 years old children [VE=84% (95%CI:77%-89%)] was higher than that in ≥6 years old children [VE=60% (95%CI: 51%-68%)]. There was no significant difference in VE among studies with different design and quality. The quality of the evidences of pooled 1-dose VE was"very low", which was downgraded in bias risk and inconsistency and not downgraded in indirectness, imprecision and publication bias. Conclusions: The 1-dose VarV can provide medium level protection for 1-12 years old children in China, but it will decrease significantly for ≥6 years old children, so it is suggested to implement the strategies of two-dose vaccination of VarV in children <6 years old. The GRADE framework can be used in the observational studies of VE and it is suggested that the technical guidelines of observational study should be worked out to improve the overall quality of evidence.


Assuntos
Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Varicela/prevenção & controle , Surtos de Doenças/prevenção & controle , Varicela/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Relação Dose-Resposta Imunológica , Humanos , Lactente , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
14.
BMC Infect Dis ; 20(1): 504, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660437

RESUMO

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.


Assuntos
Genótipo , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/genética , Rotavirus/imunologia , Vacinação , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Feminino , Gastroenterite/etiologia , Humanos , Esquemas de Imunização , Lactente , Quênia/epidemiologia , Masculino , Filogenia , Prevalência , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico
15.
Viruses ; 12(7)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674326

RESUMO

The Gammacoronavirus infectious bronchitis virus (IBV) is a highly contagious economically important respiratory pathogen of domestic fowl. Reverse genetics allows for the molecular study of pathogenic determinants to enable rational vaccine design. The recombinant IBV (rIBV) Beau-R, a molecular clone of the apathogenic Beaudette strain, has previously been investigated as a vaccine platform. To determine tissues in which Beau-R could effectively deliver antigenic genes, an in vivo study in chickens, the natural host, was used to compare the pattern of viral dissemination of Beau-R to the pathogenic strain M41-CK. Replication of Beau-R was found to be restricted to soft tissue within the beak, whereas M41-CK was detected in beak tissue, trachea and eyelid up to seven days post infection. In vitro assays further identified that, unlike M41-CK, Beau-R could not replicate at 41 °C, the core body temperature of a chicken, but is able to replicate a 37 °C, a temperature relatable to the very upper respiratory tract. Using a panel of rIBVs with defined mutations in the structural and accessory genes, viral replication at permissive and non-permissive temperatures was investigated, identifying that the Beau-R replicase gene was a determinant of temperature sensitivity and that sub-genomic mRNA synthesis had been affected. The identification of temperature sensitive allelic lesions within the Beau-R replicase gene opens up the possibility of using this method of attenuation in other IBV strains for future vaccine development as well as a method to investigate the functions of the IBV replicase proteins.


Assuntos
Infecções por Coronavirus/prevenção & controle , Vírus da Bronquite Infecciosa/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Linhagem Celular , Embrião de Galinha , Galinhas , Aves Domésticas/virologia , Doenças das Aves Domésticas/virologia , RNA Viral/genética , Temperatura , Vacinas Atenuadas/imunologia , Replicação Viral/genética , Replicação Viral/fisiologia
18.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32554697

RESUMO

Coronaviruses (CoVs) have repeatedly emerged from wildlife hosts and infected humans and livestock animals to cause epidemics with significant morbidity and mortality. CoVs infect various organs, including respiratory and enteric systems, as exemplified by newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The constellation of viral factors that contribute to developing enteric disease remains elusive. Here, we investigated CoV interferon antagonists for their contribution to enteric pathogenesis. Using an infectious clone of an enteric CoV, porcine epidemic diarrhea virus (icPEDV), we generated viruses with inactive versions of interferon antagonist nonstructural protein 1 (nsp1), nsp15, and nsp16 individually or combined into one virus designated icPEDV-mut4. Interferon-responsive PK1 cells were infected with these viruses and produced higher levels of interferon responses than were seen with wild-type icPEDV infection. icPEDV-mut4 elicited robust interferon responses and was severely impaired for replication in PK1 cells. To evaluate viral pathogenesis, piglets were infected with either icPEDV or icPEDV-mut4. While the icPEDV-infected piglets exhibited clinical disease, the icPEDV-mut4-infected piglets showed no clinical symptoms and exhibited normal intestinal pathology at day 2 postinfection. icPEDV-mut4 replicated in the intestinal tract, as revealed by detection of viral RNA in fecal swabs, with sequence analysis documenting genetic stability of the input strain. Importantly, icPEDV-mut4 infection elicited IgG and neutralizing antibody responses to PEDV. These results identify nsp1, nsp15, and nsp16 as virulence factors that contribute to the development of PEDV-induced diarrhea in swine. Inactivation of these CoV interferon antagonists is a rational approach for generating candidate vaccines to prevent disease and spread of enteric CoVs, including SARS-CoV-2.IMPORTANCE Emerging coronaviruses, including SARS-CoV-2 and porcine CoVs, can infect enterocytes, cause diarrhea, and be shed in the feces. New approaches are needed to understand enteric pathogenesis and to develop vaccines and therapeutics to prevent the spread of these viruses. Here, we exploited a reverse genetic system for an enteric CoV, porcine epidemic diarrhea virus (PEDV), and outline an approach of genetically inactivating highly conserved viral factors known to limit the host innate immune response to infection. Our report reveals that generating PEDV with inactive versions of three viral interferon antagonists, nonstructural proteins 1, 15, and 16, results in a highly attenuated virus that does not cause diarrhea in animals and elicits a neutralizing antibody response in virus-infected animals. This strategy may be useful for generating live attenuated vaccine candidates that prevent disease and fecal spread of enteric CoVs, including SARS-CoV-2.


Assuntos
Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Interferons/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Vacinas Atenuadas/imunologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/prevenção & controle , Diarreia/patologia , Diarreia/virologia , Modelos Animais de Doenças , Endorribonucleases/antagonistas & inibidores , Fezes/virologia , Íleo/patologia , Imunidade Inata , Jejuno/patologia , Pandemias , Pneumonia Viral/imunologia , Vírus da Diarreia Epidêmica Suína/genética , RNA Replicase , RNA Viral , Suínos , Doenças dos Suínos/virologia , Células Vero , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
19.
mBio ; 11(3)2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561657

RESUMO

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Humanos , Sarampo/imunologia , Caxumba/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/patologia , Rubéola (Sarampo Alemão)/imunologia , Vacinação
20.
Lancet Infect Dis ; 20(10): 1193-1203, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32497524

RESUMO

BACKGROUND: Chikungunya disease, which results in incapacitating arthralgia, has been reported worldwide. We developed a live-attenuated chikungunya virus (CHIKV) vaccine candidate designed for active immunisation of the general population living in endemic regions, as well as serving as a prophylactic measure for travellers to endemic areas. METHODS: This single-blind, randomised, dose-escalation, phase 1 study investigated as primary outcome safety of a live-attenuated CHIKV vaccine candidate. At two professional clinical trial centres in Illinois and Alabama, USA, healthy volunteers aged 18-45 years were randomly assigned (1:1:2) to one of three escalating dose groups (low dose 3·2 × 103 per 0·1 mL; medium dose 3·2 × 104 per 1 mL; or high dose 3·2 × 105 50% tissue culture infection dose per 1 mL) and received a single-shot immunisation on day 0. Individuals in all groups were revaccinated with the highest dose on either month 6 or 12, and followed up for 28 days after revaccination. The safety analysis included all individuals who received the single vaccination; the immunogenicity analysis, which was a secondary outcome, included all individuals who completed the study without major protocol deviations (per-protocol population). The study is registered with ClinicalTrials.gov, NCT03382964, and is complete. FINDINGS: The study was done between March 5, 2018, and Jul 23, 2019, with 120 adults recruited and enrolled between March 5 and June 21, 2018, and assigned to receive a low (n=31), medium (n=30), or high (n=59) dose of the vaccine. The vaccine was safe in the high-dose group and well tolerated in the low-dose and medium-dose groups. Four (7%) of 59 vaccinees in the high-dose group reported any local reaction, and 11 (36%), 12 (40%), and 40 (68%) volunteers in the low-dose, medium-dose, and high-dose groups, respectively, reported any solicited systemic reaction. No vaccine-related serious adverse events were reported. Data up to month 12 after a single immunisation of the 120 healthy volunteers showed a good immunogenicity profile with 100% seroconversion rates achieved at day 14 (103 [100%] of 103) and sustained for 1 year across all dose groups. Mean peak antibody titres at day 28 ranged from 592·6 to 686·9 geometric mean titres from the low-dose to high-dose groups, respectively. A single vaccination was sufficient to induce sustaining high-titre neutralising antibodies, as shown by the absence of an anamnestic response after any revaccination ranging from 94% to 100% of participants. Following revaccination, vaccinees were protected from vaccine-induced viraemia. INTERPRETATION: A novel live-attenuated CHIKV vaccine was well tolerated and highly immunogenic in an adult population and could be an effective intervention for prophylaxis of chikungunya disease worldwide. FUNDING: Valneva, Vienna, Austria; Coalition for Epidemic Preparedness Innovation and EU Horizon 2020.


Assuntos
Febre de Chikungunya/prevenção & controle , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Feminino , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Vacinas Atenuadas/imunologia , Vacinas Virais/efeitos adversos , Adulto Jovem
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