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1.
Clin Infect Dis ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31734699

RESUMO

BACKGROUND: Evaluation of a licensed inactivated EV71 vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label and controlled trial involving a large population of 155,995 children aged 6-71 months is performed; 40,724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected hand, foot and mouth disease (HFMD) cases were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th days post inoculation through the local database of Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71 infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval [CI], 24.0 to 98.6) vaccine effectiveness (VE) against EV71 infection and a 4.58% rate of reported AEs were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

2.
Vaccine ; 37(40): 5909-5919, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31447125

RESUMO

The Developing Countries Vaccine Manufacturers Network (DCVMN) convened vaccine manufacturing experts and leaders from local and global public health organizations for its 19th Annual General Meeting. Lectures and panel discussions centered on international cooperation for better access to vaccines, and partnerships in areas ranging from vaccine research and process development, to clinical studies, regulatory, supply chain and emergency preparedness and response. Global vaccine market trends and changes that will impact vaccine financing and procurement methods were discussed as well as capital sources, including funding, for the development of new or improved vaccines. DCVMN members presented their progress in developing novel Hexavalent, Meningitis, Pneumococcal Conjugate Vaccine, Shigella, Mumps, Rotavirus, Yellow Fever, Polio, Hepatitis E and Dengue vaccines, and a novel monoclonal antibody cocktail for post-bite prophylaxis against rabies infections. Access to and availability of vaccines is enhanced through sharing of best practices for vaccine quality control, reducing redundant testing and promoting development of harmonized common standards. Eligible stakeholders were encouraged to join the WHO-National Control Laboratory Network for Biologicals which serves as a platform for collaboration and technical exchange in this area. Increasing regulatory convergence at the regional and global levels through mechanisms such as joint dossier review and the WHO Collaborative Registration Procedure can help to accelerate vaccine access globally. Additionally, four proposals for streamlining procedures and alignment of dossiers were discussed. Successful partnerships between a broad range of stakeholders, including international organizations, manufacturers, academic research institutes and regulators have provided support for, and in some cases accelerated, vaccine innovation, clinical trials and registration, WHO prequalification, vaccine introduction and access. Strong partnerships, based on experience and trust, help leverage opportunities and are critically important to advancing the shared goal of providing quality vaccines for all people.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(5): 441-444, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31104659

RESUMO

OBJECTIVE: To investigate the epidemiological characteristics of mumps in mainland China from 2004 to 2018, and to provide data for the key population for prevention and control of mumps. METHODS: The epidemiological characteristics of mumps were analyzed with reference to the data of the cases of mumps reported in the National Scientific Data Sharing Platform for Population and Health and Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China. Descriptive epidemiology was used to analyze the epidemiological characteristics of mumps. RESULTS: A total of 4 272 368 cases of mumps were reported in China during 2004-2018, with an average annual reported incidence rate of 21.44/100 000. A single dose of mumps-containing vaccine was added to the national Expanded Program of Immunization in 2008, but the annual incidence rate ranged from 12.84/100 000 to 35.59/100 000. The second dose of measles, mumps and rubella combined attenuated live vaccine was included in the routine immunization in Beijing, Tianjin and Shanghai, and then the average incidence rate of mumps reported in these three regions dropped to about 10/100 000. From 2004 to 2016, the population aged 3-14 years accounted for 81.16% of all patients with mumps. The children aged 6 years had the highest incidence rate of mumps during 2004-2013. CONCLUSIONS: A single dose of mumps-containing vaccine has no obvious effect on the incidence rate of mumps. Children aged 6 years have the highest incidence rate of mumps. A booster dose of mumps-containing vaccine should be given to preschool children.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Adolescente , Criança , Pré-Escolar , China , Humanos , Vacina contra Caxumba
4.
J Infect Dis ; 219(1): 50-58, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085178

RESUMO

Background: Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods: A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results: Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions: The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.


Assuntos
Vacina contra Caxumba/administração & dosagem , Vírus da Caxumba/imunologia , Caxumba/prevenção & controle , Anticorpos Antivirais/sangue , Pré-Escolar , China/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Genótipo , Testes de Inibição da Hemaglutinação , Humanos , Imunização , Lactente , Masculino , Caxumba/imunologia , Vacina contra Caxumba/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
5.
BMC Immunol ; 19(1): 4, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29368591

RESUMO

BACKGROUND: The Haemophilus influenzae type b (Hib) conjugate vaccine has been widely used in children to prevent invasive Hib disease because of its strong immunogenicity and antibody response induction relative to the capsular polysaccharide (CPS) antigen. The data from vaccine studies suggest that the conjugate vaccine contains carrier proteins that enhance and/or regulate the antigen's immunogenicity, but the mechanism of this enhancement remains unclear. METHODS: To explore the immunological role of the conjugate vaccine, we compared the immune responses and gene profiles of rhesus macaques after immunization with CPS, carrier protein tetanus toxoid (TT) or conjugate vaccine. RESULTS: A distinct immune response was induced by the Hib conjugate vaccine but not by CPS or carrier protein TT. The genes that were dynamically regulated in conjunction with the macaque immune responses to the conjugate vaccine were investigated. CONCLUSIONS: We propose that these genes are involved in the induction of specific immunity that is characterized by the appearance and maintenance of antibodies against Hib.


Assuntos
Haemophilus influenzae tipo b/imunologia , Leucócitos Mononucleares/imunologia , Macaca mulatta/imunologia , Toxoide Tetânico/imunologia , Transcriptoma/imunologia , Vacinação/métodos , Vacinas Conjugadas/imunologia , Animais , Cápsulas Bacterianas/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Imunidade/genética , Imunidade/imunologia , Leucócitos Mononucleares/metabolismo , Macaca mulatta/genética , Polissacarídeos Bacterianos/imunologia , Transcriptoma/genética , Vacinas Conjugadas/administração & dosagem
6.
Clin Infect Dis ; 64(10): 1317-1325, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28419204

RESUMO

Background: A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Methods: Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. Results: All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Conclusions: Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. Clinical Trials Registration: NCT01056705.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Soros Imunes/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/imunologia , Poliovirus/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Relação Dose-Resposta Imunológica , Humanos , Lactente , Testes de Neutralização , Poliomielite/prevenção & controle , Poliomielite/transmissão , Poliomielite/virologia , Poliovirus/genética , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Análise de Sequência de DNA , Vacinação
7.
Virology ; 500: 198-208, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27829175

RESUMO

Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-γ-specific memory T-cells in macaques infected with CV-A16. Furthermore, existing neutralizing antibodies in macaques immunized with the inactivated vaccine were surprisingly unable to protect against a viral challenge despite the presence of a positive T-cell memory response against viral antigens. The virus was capable of infecting pre-conventional dendritic cells and replicating within them, which may correlate with the immunological characteristics observed in the animals.


Assuntos
Enterovirus Humano A/fisiologia , Doença de Mão, Pé e Boca/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Modelos Animais de Doenças , Enterovirus Humano A/genética , Enterovirus Humano A/patogenicidade , Doença de Mão, Pé e Boca/patologia , Doença de Mão, Pé e Boca/prevenção & controle , Doença de Mão, Pé e Boca/virologia , Humanos , Interferon gama/imunologia , Macaca mulatta , Testes de Neutralização , Linfócitos T/imunologia , Vacinas Virais/imunologia
8.
J Infect Dis ; 214(11): 1728-1734, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27658691

RESUMO

BACKGROUND: The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. METHODS: In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. RESULTS: Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. CONCLUSIONS: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.


Assuntos
Anticorpos Antivirais/sangue , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Método Duplo-Cego , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/efeitos adversos
9.
Virol J ; 13: 152, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27618986

RESUMO

BACKGROUND: UL7, a tegument protein of Herpes Simplex Virus type I (HSV-1), is highly conserved in viral infection and proliferation and has an unknown mechanism of action. METHODS: A HSV-1 UL7 mutant (UL7-MU) was constructed using the CRISPR-cas9 system. The replication rate and plaque morphology were used to analyze the biological characteristics of the wild-type (WT), UL7-MU and MU-complemented P1 viruses. The virulence of the viruses was evaluated in mice. Real-time RT-qPCR and ChIP assays were used to determine the expression levels of relevant genes. RESULTS: The replication capacity of a recombinant virus (UL7-MU strain) was 10-fold lower than that of the WT strain. The neurovirulence and pathologic effect of the UL7-MU strain were attenuated in infected mice compared with the WT strain. In the latency model, the expression of latency-associated transcript (LAT) in the central nervous system (CNS) and trigeminal nerve was lower in UL7-MU-infected mice than in WT strain-infected mice. The transcription level of the immediate-early gene α-4 in UL7-MU-infected cells was reduced by approximately 2-fold compared with the clear transcriptional peak identified in WT strain-infected Vero cells within 7 h post-infection (p.i.). CONCLUSION: By modulating the transcription of the α-4 gene, UL7 may be involved in transcriptional regulation through its interaction with the transcript complex structure of the viral genome during HSV-1 infection.


Assuntos
Herpes Simples/virologia , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidade , Proteínas Imediatamente Precoces/genética , Proteínas da Matriz Viral/genética , Animais , Regulação Viral da Expressão Gênica , Herpesvirus Humano 1/genética , Humanos , Proteínas Imediatamente Precoces/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas da Matriz Viral/metabolismo , Virulência
10.
Glob Pediatr Health ; 3: 2333794X16643723, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27336013

RESUMO

Hand, foot, and mouth disease (HFMD), with vesiculae on the hands, feet and mouth, is an infectious disease caused by many viral pathogens. However, the differences of immune response induced by these pathogens are unclear. We compared the clinical manifestations and the levels of immunologic indicators from 60 HFMD patients caused by different viral pathogens to analyze the differences in the immune response. It was shown that Th2 cytokines (IL-4 and IL-10) increased significantly in EV71-infected children; Th1 cytokines (IL-2 and IFN-γ) rose in CA16-infected children; both Th1 and Th2 cytokines elevated in non-EVG-infected children; only individual cytokines (such as IL-10) went up in EVG-infected children. Meanwhile, the antibodies induced by viral infection could not cross-interfere between the different pathogens. These differences might be due to variations in the immune response induced by the individual pathogens or to the pathogenesis of the infections by the individual pathogens.

11.
Virol J ; 13: 108, 2016 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-27343062

RESUMO

Herpes simplex virus 1 (HSV-1) is composed of complex structures primarily characterized by four elements: the nucleus, capsid, tegument and envelope. The tegument is an important viral component mainly distributed in the spaces between the capsid and the envelope. The development of viral genome editing technologies, such as the identification of temperature-sensitive mutations, homologous recombination, bacterial artificial chromosome, and the CRISPR/Cas9 system, has been shown to largely contribute to the rapid promotion of studies on the HSV-1 tegument protein. Many researches have demonstrated that tegument proteins play crucial roles in viral gene regulatory transcription, viral replication and virulence, viral assembly and even the interaction of the virus with the host immune system. This article briefly reviews the recent research on the functions of tegument proteins and specifically elucidates the function of tegument proteins in viral infection, and then emphasizes the significance of using genome editing technology in studies of providing new techniques and insights into further studies of HSV-1 infection in the future.


Assuntos
Edição de Genes , Técnicas Genéticas , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Proteínas Estruturais Virais/genética , Animais , Técnicas Genéticas/tendências , Genoma Viral , Herpesvirus Humano 1/metabolismo , Humanos , Proteínas Estruturais Virais/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-28066727

RESUMO

The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.


Assuntos
Astrócitos/virologia , Encéfalo/virologia , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/virologia , Tropismo Viral , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Enterovirus Humano A/crescimento & desenvolvimento , Enterovirus Humano A/isolamento & purificação , Epinefrina/metabolismo , Humanos , Macaca mulatta , Norepinefrina/metabolismo
13.
Vaccine ; 33(46): 6290-7, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26419198

RESUMO

During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.


Assuntos
Modelos Animais de Doenças , Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas Virais/imunologia , Animais , Animais Recém-Nascidos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/patologia , Humanos , Lactente , Interferon gama/metabolismo , Macaca mulatta , Masculino , Placebos/administração & dosagem , Linfócitos T/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem
14.
Intervirology ; 58(4): 260-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26517705

RESUMO

OBJECTIVES: To investigate the biological characteristics of the two types of virion fractions of Coxsackievirus A 16 (CA16), which include the real virion fraction and pseudo-virion fraction in their structure, pathogenicity and immunogenicity. METHODS: We obtained the two CA16 virion fractions by density gradient centrifugation. The morphology of virion fractions was analyzed by electron microscopy, while the antigenic characteristics and immunogenicity of two virion fractions were determined by ELISA, SDS-PAGE, Western blot, qRT-PCR, and the mouse model of immune response. RESULTS: The two virion fractions contained the major viral antigen components in their structures, showed similar pathogenicity in a neonatal murine model and were capable of inducing an effective primary immune response in adult mice, regardless of the essential distinction between the two virion fractions, which was the cleavage of VP0 to VP2 and VP4. CONCLUSIONS: The two CA16 virion fractions showed antigenicity and immunogenicity with inducing a specific immune response in animals.


Assuntos
Antígenos Virais/imunologia , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Vírion/química , Vírion/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Encéfalo/virologia , Células Cultivadas , Centrifugação com Gradiente de Concentração , Modelos Animais de Doenças , Eletroforese em Gel de Poliacrilamida , Enterovirus Humano A/imunologia , Pulmão/ultraestrutura , Pulmão/virologia , Camundongos , Vírion/isolamento & purificação , Vírion/patogenicidade , Virulência
15.
J Clin Virol ; 72: 25-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26361010

RESUMO

Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens.


Assuntos
Coinfecção/diagnóstico , Coinfecção/patologia , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/patologia , Poliovirus/isolamento & purificação , Pré-Escolar , Humanos , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
16.
BMC Med ; 13: 226, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26381232

RESUMO

BACKGROUND: To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy. METHODS: A sub-cohort of 1,100 volunteers from Guangxi Province in China was eligible for enrolment and randomly administered either the EV71 vaccine or a placebo on days 0 and 28 in a phase III clinical trial and then observed for the following 2 years with approval by an independent ethics committee of Guangxi Zhuang Autonomous Region, China. Serum samples from the 350 participants who provided a full series of blood samples (at all the sampling points) within the 2-year period were collected. Vaccine-induced immune effects, including the neutralizing antibody titres and cross-protection against different genotypes of EV71, were examined. This study also evaluated the protective efficacy of this vaccine based upon clinical diagnosis. RESULTS: This sub-cohort showed a >60% drop-out rate over 2 years. The seroconversion rates among the 161 immunized subjects remained >95% at the end of study. The geometric mean titres of neutralizing antibodies (anti-genotype C4) 360 days after vaccination in 350 subjects were 81.0 (subjects aged 6-11 months), 98.4 (12-23 months), 95.0 (24-35 months), and 81.8 (36-71 months). These titres subsequently increased to 423.1, 659.0, 545.0, and 321.9, respectively, at 540 days post-immunization (d.p.i.), and similar levels were maintained at 720 d.p.i. Higher IFN-γ/IL-4-specific responses to the C4 genotype of EV71 and cross-neutralization reactivity against major EV71 genotype strains were observed in the vaccine group compared to those in the placebo group. Five EV71-infected subjects were observed in the placebo-treated control group and none in the vaccine-immunized group in per-protocol analysis. CONCLUSION: These results are consistent with the induction of dynamic immune responses and protective efficacy of the vaccine against most circulating EV71 strains. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT01569581, Trial registration date: March 2012.


Assuntos
Infecções por Enterovirus/prevenção & controle , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/administração & dosagem , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Pré-Escolar , China , Proteção Cruzada , Método Duplo-Cego , Enterovirus Humano A/imunologia , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
17.
Virology ; 464-465: 1-10, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25036476

RESUMO

During HSV-1 infection, the viral UL31 protein forms a complex with the UL34 protein at the cellular nuclear membrane, where both proteins play important roles in the envelopment of viral nucleocapsids and their egress into the cytoplasm. To characterize the mechanism of HSV-1 nucleocapsid egress, we screened host proteins to identify proteins that interacted with UL31 via yeast two-hybrid analysis. Transmembrane protein 140 (TMEM140), was identified and confirmed to bind to and co-localize with UL31 during viral infection. Further studies indicated that TMEM140 inhibits HSV-1 proliferation through selectively blocking viral nucleocapsid egress during the viral assembly process. The blockage function of TMEM140 is mediated by impeding the formation of the UL31-UL34 complex due to competitive binding to UL31. Collectively, these data suggest the essentiality of the UL31-UL34 interaction in the viral nucleocapsid egress process and provide a new anti-HSV-1 strategy in viral assembly process of nucleocapsid egress.


Assuntos
Proteínas de Transporte/metabolismo , Herpes Simples/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Nucleocapsídeo/metabolismo , Proteínas Virais/metabolismo , Liberação de Vírus , Sequência de Aminoácidos , Proteínas de Transporte/genética , Herpes Simples/genética , Herpesvirus Humano 1/química , Herpesvirus Humano 1/genética , Humanos , Proteínas de Membrana/genética , Dados de Sequência Molecular , Proteínas Nucleares/química , Proteínas Nucleares/genética , Nucleocapsídeo/genética , Ligação Proteica , Alinhamento de Sequência , Proteínas Virais/química , Proteínas Virais/genética , Montagem de Vírus
18.
Vaccine ; 32(35): 4436-42, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-24958699

RESUMO

Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection.


Assuntos
Infecções por Coxsackievirus/imunologia , Enterovirus Humano A/imunologia , Enterovirus/imunologia , Vacinas Virais/imunologia , Animais , Temperatura Corporal , Citocinas/sangue , Modelos Animais de Doenças , Macaca mulatta , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Viremia , Eliminação de Partículas Virais
19.
Hum Vaccin Immunother ; 10(5): 1266-73, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24583556

RESUMO

The coxsackie A16 virus (CA16), along with enterovirus 71 (EV71), is a primary pathogen that causes hand, foot, and mouth disease (HFMD). To control HFMD, CA16, and EV71 vaccines are needed. In this study, an experimental inactivated CA16 vaccine was prepared using human diploid cells, and the vaccine's immunogenicity was analyzed in mice and rhesus monkeys. The results showed that the neutralizing antibody was developed in a dose-dependent manner, and was sustained for 70 days with an average GMT (geometric mean titer) level of 80 to 90 in immunized mouse and for 56 days with GMT of higher than 300 in monkeys. The neutralizing antibody had a cross-neutralizing activity against different viral strains (genotype A and B), and the specific IFN-γ-secreting cell response was activated by these virus strains in an ELISPOT assay. This study provides evidence for the potential use of inactivated CA16 as a candidate for use in vaccines.


Assuntos
Diploide , Enterovirus/imunologia , Fenômenos Imunogenéticos/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Animais , Linhagem Celular , Feminino , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Haplorrinos , Humanos , Fenômenos Imunogenéticos/efeitos dos fármacos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos ICR , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/administração & dosagem
20.
Hum Vaccin Immunother ; 10(5): 1382-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24614759

RESUMO

BACKGROUND: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. METHODS: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. RESULTS: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. CONCLUSIONS: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.


Assuntos
Fenômenos Imunogenéticos/imunologia , Vacina contra Caxumba/efeitos adversos , Vacina contra Caxumba/imunologia , Caxumba/imunologia , Caxumba/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Tosse/induzido quimicamente , Tosse/imunologia , Feminino , Humanos , Fenômenos Imunogenéticos/efeitos dos fármacos , Lactente , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Eliminação de Partículas Virais/efeitos dos fármacos , Eliminação de Partículas Virais/imunologia , Adulto Jovem
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