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2.
J Zoo Wildl Med ; 50(4): 972-975, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926530

RESUMO

This study evaluated the safety of and humoral response to the Merial Recombitek® recombinant canine distemper virus (rCDV) vaccine in maned wolves (n = 9, age 2-9 yr). All maned wolves had prior history of annual vaccination with the Merial Purevax® ferret rCDV vaccine. Serum neutralization (SN) to CDV was measured prior to initial vaccination with the rCDV Recombitek vaccine followed by a booster vaccination at 4-6 wk. Final SN titers were obtained at 13 wk post initial vaccination. The maned wolves developed no observable adverse side effects through the study. Pre-Recombitek vaccination SN titers ranged from negative to 1: 8. Postvaccination CDV titers ranged from negative to 1: 8, and were therefore below the range of that considered protective in domestic dogs.


Assuntos
Anticorpos Antivirais/sangue , Canidae , Vírus da Cinomose Canina/imunologia , Cinomose/prevenção & controle , Vacinas Virais/imunologia , Animais , Feminino , Masculino , Vacinas Virais/efeitos adversos
3.
Nat Commun ; 10(1): 5677, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831806

RESUMO

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.


Assuntos
Imunidade , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Gravidez , Linfócitos T/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/efeitos adversos , Vacinas Virais/uso terapêutico , Zika virus/genética , Infecção por Zika virus/virologia
4.
PLoS Negl Trop Dis ; 13(4): e0007316, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31026260

RESUMO

INTRODUCTION: Chikungunya virus (CHIKV) is a re-emerging pathogen responsible for causing outbreaks of febrile disease accompanied with debilitating joint pain. Symptoms typically persist for two weeks, but more severe and chronic chikungunya illnesses have been reported, especially in the elderly. Currently, there are no licensed vaccines or antivirals against CHIKV available. In this study, we combined a CHIK virus-like particle (VLP) vaccine with different adjuvants to enhance immunogenicity and protection in both, adult and aged mice. METHODS: CHIK VLP-based vaccines were tested in 6-8-week-old (adult) and 18-24-month-old (aged) female C57BL/6J mice. Formulations contained CHIK VLP alone or adjuvants: QuilA, R848, or Imject Alum. Mice were vaccinated three times via intramuscular injections. CHIKV-specific antibody responses were characterized by IgG subclass using ELISA, and by microneutralization assays. In addition, CHIKV infections were characterized in vaccinated and non-vaccinated adult mice and compared to aged mice. RESULTS: In adult mice, CHIKV infection of the right hind foot induced significant swelling, which peaked by day 7 post-infection at approximately 170% of initial size. Viral titers peaked at 2.53 × 1010 CCID50/ml on day 2 post-infection. Mice vaccinated with CHIK VLP-based vaccines developed robust anti-CHIKV-specific IgG antibody responses that were capable of neutralizing CHIKV in vitro. CHIK VLP alone or CHIK plus QuilA administered by IM injections protected 100% of mice against CHIKV. In contrast, the antibody responses elicited by the VLP-based vaccines were attenuated in aged mice, with negligible neutralizing antibody titers detected. Unvaccinated, aged mice were resistant to CHIKV infection, while vaccination with CHIKV VLPs exacerbated disease. CONCLUSIONS: Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in the aged.


Assuntos
Febre de Chikungunya/induzido quimicamente , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/crescimento & desenvolvimento , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas Virais/efeitos adversos , Adjuvantes Imunológicos/administração & dosagem , Fatores Etários , Compostos de Alúmen/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina G/sangue , Injeções Intramusculares , Camundongos Endogâmicos C57BL , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas Virais/administração & dosagem
5.
mBio ; 10(2)2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015334

RESUMO

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is one of the most medically important tick-borne pathogens of the Old World. Despite decades of active research, attempts to develop of a live attenuated virus (LAV) vaccine against TBEV with acceptable safety and immunogenicity characteristics have not been successful. To overcome this impasse, we generated a chimeric TBEV that was highly immunogenic in nonhuman primates (NHPs). The chimeric virus contains the prM/E genes of TBEV, which are expressed in the genetic background of an antigenically closely related, but less pathogenic member of the TBEV complex-Langat virus (LGTV), strain T-1674. The neurovirulence of this chimeric virus was subsequently controlled by robust targeting of the viral genome with multiple copies of central nervous system-enriched microRNAs (miRNAs). This miRNA-targeted T/1674-mirV2 virus was highly stable in Vero cells and was not pathogenic in various mouse models of infection or in NHPs. Importantly, in NHPs, a single dose of the T/1674-mirV2 virus induced TBEV-specific neutralizing antibody (NA) levels comparable to those seen with a three-dose regimen of an inactivated TBEV vaccine, currently available in Europe. Moreover, our vaccine candidate provided complete protection against a stringent wild-type TBEV challenge in mice and against challenge with a parental (not miRNA-targeted) chimeric TBEV/LGTV in NHPs. Thus, this highly attenuated and immunogenic T/1674-mirV2 virus is a promising LAV vaccine candidate against TBEV and warrants further preclinical evaluation of its neurovirulence in NHPs prior to entering clinical trials in humans.IMPORTANCE Tick-borne encephalitis virus (TBEV) is one of the most medically important tick-borne pathogens of the Old World. Despite decades of active research, efforts to develop of TBEV live attenuated virus (LAV) vaccines with acceptable safety and immunogenicity characteristics have not been successful. Here we report the development and evaluation of a highly attenuated and immunogenic microRNA-targeted TBEV LAV.


Assuntos
Anticorpos Antivirais/sangue , Portadores de Fármacos , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/prevenção & controle , Vetores Genéticos , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Vírus da Encefalite Transmitidos por Carrapatos/crescimento & desenvolvimento , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/imunologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/genética , Replicação Viral
6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(3): 252-257, 2019 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-30841662

RESUMO

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion: The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Enterovirus/imunologia , Vigilância de Produtos Comercializados , Vacinas Virais/efeitos adversos , Animais , Criança , China/epidemiologia , Infecções por Enterovirus/prevenção & controle , Humanos , Vacinas de Produtos Inativados/efeitos adversos , Células Vero
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(3): 258-261, 2019 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-30841663

RESUMO

Objective: To evaluate the post-marketing safety of inactivated Enterovirus type 71 (EV-A71) vaccine (human diploid cell) . Methods: A total of 20 191 healthy children aged 6 to 59 months were invited to receive 2 doses of EV-A71 vaccine in Zhejiang Province from September 2016 to December 2017. Child caregivers were followed up on the 4(th) or 5(th) day after each EV-A71 vaccination, and the incidence of local, systemic, and other adverse events within 3 days after vaccination was recorded to assess vaccine safety. Describe the differences in adverse events among children with different characteristics. Results: A total of 32 230 doses were observed in this study, of which 20 191 and 12 039 were vaccinated for the first and the second dose, respectively; and the incidence of adverse events within 3 days was 2.045% (413 doses) and 1.611% (194 doses), respectively. After the first and the second dose, the number of systemic adverse events was the highest, 371 and 175 cases, respectively, with an incidence of 1.837% and 1.454%, respectively; the number of local adverse events was the lowest, 14 and 2 doses, respectively, with an incidence of 0.069% and 0.017%. Local adverse events occurred after vaccination were generally mild, and only 2 patients had level of 3; among the systemic adverse events, 39 patients had a fever level of 3 or higher, accounting for 8.2% of the total fever. Most of the symptoms in the local adverse events did not require treatment, only 3 cases of vaccination site rash and 2 cases of pruritus were self-purchased drugs or outpatient treatment; except for 5 cases of fever, the other symptoms were not hospitalized in the case of systemic adverse events. Conclusion: The incidence of adverse events within 3 days after vaccination with EV-A71 vaccine was low in children, mainly systemic adverse events, and the prognosis was good.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Enterovirus Humano A/imunologia , Vigilância de Produtos Comercializados , Vacinas Virais/efeitos adversos , Pré-Escolar , China/epidemiologia , Diploide , Infecções por Enterovirus/prevenção & controle , Humanos , Lactente , Vacinas de Produtos Inativados/efeitos adversos
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(3): 262-266, 2019 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-30841664

RESUMO

Objectives: To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community. Methods: We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher's exact test were used to compare the difference of AEs incidence in various characteristics among two groups. Results: A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively. Conclusion: Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Enterovirus Humano A/imunologia , Vigilância de Produtos Comercializados , Vacinas Virais/efeitos adversos , Pré-Escolar , China/epidemiologia , Infecções por Enterovirus/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Vacinas de Produtos Inativados/efeitos adversos
9.
PLoS One ; 14(2): e0211158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730935

RESUMO

Attenuated live infectious laryngotracheitis (ILT) virus (ILTV) vaccines have been used to prevent and control the outbreak of ILT worldwide. Recent studies using high-throughput sequencing technology have increased the number of complete genome sequences of ILTVs, enabling comparative genome analysis. Although 37 complete genome sequences of ILTV, including vaccine strains, have been reported, the complete genome sequence of any field strain of ILTV in South Korea is yet to be published. In this study, we determined and analyzed the complete genome sequences of three virulent Korean field strains of ILTV (40798/10/Ko, 0206/14/Ko, and 30678/14/Ko). Two of the Korean field strains (40798/10/Ko and 0206/14/Ko) displayed fewer non-synonymous single nucleotide polymorphisms than those of the Serva vaccine strain, indicating that these Korean field strains of ILTV most likely originated from the vaccine strain. The third ILTV strain, 307678/14/Ko, had two regions in the genome showing recombination between the Serva vaccine-like strain and the Australian A20 vaccine-like strain. Comparative genome analysis of ILTV using the Korean field strains with variable virulence can shed light on the recent trend of the emergence of virulent ILTV strains in the field. A few amino acid changes in the genome of ILTV vaccines could enhance the virulence in the vaccine strain, and natural recombination should be considered one of the major risks for the generation of revertant strains of ILTV under field conditions.


Assuntos
Galinhas/virologia , Infecções por Herpesviridae/veterinária , Herpesvirus Galináceo 1/genética , Doenças das Aves Domésticas/virologia , Animais , Hibridização Genômica Comparativa , DNA Viral/genética , Genoma Viral , Infecções por Herpesviridae/virologia , Herpesvirus Galináceo 1/isolamento & purificação , Herpesvirus Galináceo 1/patogenicidade , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Polimorfismo de Nucleotídeo Único , Recombinação Genética , República da Coreia , Alinhamento de Sequência , Análise de Sequência de DNA , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/genética , Vacinas Virais/efeitos adversos , Vacinas Virais/genética , Virulência/genética
11.
J Infect Dis ; 220(1): 46-56, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-30796818

RESUMO

BACKGROUND: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. METHODS: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. RESULTS: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. CONCLUSIONS: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. CLINICAL TRIALS REGISTRATION: NCT02376400.


Assuntos
Formação de Anticorpos/imunologia , Vacinas contra Ebola/efeitos adversos , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Surtos de Doenças/prevenção & controle , Feminino , Voluntários Saudáveis , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Tanzânia , Uganda , Vacinação/efeitos adversos , Vacinas Virais/efeitos adversos , Adulto Jovem
12.
Poult Sci ; 98(1): 105-111, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690611

RESUMO

Ornithobacterium rhinotracheale (ORT), a bacterium causing respiratory tract infection, has led to a significant problem in the intensive poultry production in Egypt. Polymerase chain reaction-amplified 784-bp specific ORT DNA fragments were found in 7 ORT isolates from lungs, air sacs, and tracheas of commercial broilers or layers in Egypt in 2015. The objective of this study was to investigate the role of the live variant IBV 4/91 with ORT infection. A total of 120 14-d-old broiler chickens (Cobb 500) were equally divided into 4 groups for experimental infection in a complete randomized design. Group 1 was infected with ORT strain and live infectious bronchitis vaccine (IBV 4/91) simultaneously; group 2 was infected with the bacterial strain alone; group 3 was vaccinated only with IBV 4/91, and group 4 was the non-vaccinated and non-infected control group. The respiratory signs, post-mortem lesions (tracheitis and pneumonia) and histopathological findings of lungs, trachea, and air sacs in the experimentally infected broiler chickens appeared to be more prominent in the chickens of group 1 than group 2. With respect to body weight, weight gain, feed conversion rate, and Ornithobacterium re-isolation, there was a difference (P ≤ 0.05) among the chickens of group 1 and the other groups. This reveals that the use of live infectious bronchitic vaccines, which is a common practice in the local Egyptian field of production, may concomitantly increase the pathogenicity of ORT in broiler chickens.


Assuntos
Infecções por Flavobacteriaceae/veterinária , Ornithobacterium/patogenicidade , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/virologia , Vacinas Virais/administração & dosagem , Animais , Galinhas , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Egito , Infecções por Flavobacteriaceae/patologia , Vírus da Bronquite Infecciosa/imunologia , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos
13.
Expert Rev Pharmacoecon Outcomes Res ; 19(4): 473-482, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30468095

RESUMO

ABSTRACT  Background: Zika virus is a newly emerging infection, associated with increasingly large outbreaks especially in tropical countries such as Brazil. A future Zika vaccine can contribute to decreasing the number of cases and associated complications. Information about consumers' willingness to pay (WTP) for a hypothetical Zika vaccine can help price setting discussions in the future in Brazil, starting with the private market. METHODS: A cross-sectional study conducted among residents of Minas Gerais, Brazil, regarding their WTP for a hypothetical Zika Vaccine. The mean effective protection was 80%, with the possibility of some local and systemic side- effects. RESULTS: 517 people were interviewed. However, 28 would not be vaccinated even if the vaccine was free. Most of the resultant interviewees (489) were female (58.2%), had completed high school (49.7%), were employed (71.2%), had private health insurance (52.7%), and did not have Zika (96.9%). The median individual maximum WTP for this hypothetical Zika vaccine (one dose) was US$31.34 (BRL100.00). CONCLUSION: Such discussions regarding WTP can contribute to decision-making about prices once a Zika vaccine becomes available in Brazil alongside other ongoing programs to control the virus.


Assuntos
Financiamento Pessoal/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Vacinas Virais/administração & dosagem , Infecção por Zika virus/prevenção & controle , Adulto , Brasil , Estudos Transversais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Vacinas Virais/efeitos adversos , Vacinas Virais/economia , Adulto Jovem , Infecção por Zika virus/economia
14.
Acta Trop ; 190: 193-203, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30472082

RESUMO

This study was conducted to evaluate an adjuvant, Montanide (IMS 3015), in improving the quality of Rift Valley fever (RVF) vaccine relative to the traditional adjuvant, aluminum hydroxide gel. Vaccinated sheep were evaluated using biochemical analysis, kidney function tests, liver function tests, and immunological tests. Sheep vaccinated with Montanide (IMS 3015) adjuvant showed significantly higher total protein, total globulin, and gamma globulin concentrations from the second week until the fifth month than the controls. Conversely, albumin concentration and the A/G ratio significantly decreased during this period. Kidney function and liver function tests revealed no differences among any of the groups. There was a significant increase in lymphocyte proportion and a decrease in neutrophil proportion in sheep vaccinated with the Montanide (IMS 3015) adjuvant. Lymphocyte cell proliferation was significantly different in sheep vaccinated with the Montanide (IMS 3015) adjuvant from that in controls. Neutralizing indices were significantly higher in sheep vaccinated with the Montanide (IMS 3015) adjuvant than in controls. The current study showed that sheep vaccinated with inactivated RVF virus with Montanide (IMS 3015) as an adjuvant were protected and no pathological symptoms or biochemical changes were detected. Moreover, the vaccine induced rapid onset of immunological responses with long durations unlike inactivated RVF vaccine with aluminum hydroxide gel.


Assuntos
Adjuvantes Imunológicos , Vírus da Febre do Vale do Rift/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais , Proliferação de Células , Rim/fisiologia , Fígado/fisiologia , Contagem de Linfócitos , Linfócitos/fisiologia , Camundongos , Neutrófilos , Albumina Sérica/metabolismo , Ovinos , Vacinas Virais/efeitos adversos , gama-Globulinas/metabolismo
15.
J Vet Diagn Invest ; 31(1): 107-112, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30541417

RESUMO

In late summer 2017, we observed acute, fatal cases of bovine viral diarrhea in captive Rocky Mountain bighorn sheep ( Ovis canadensis canadensis) in Colorado following use of a contaminated modified-live bluetongue virus vaccine. Following vaccination, at least 14 of 28 (50%) vaccinated bighorn sheep developed hemorrhagic diarrhea, and 6 of 28 (21%) vaccinated bighorn sheep died. Autopsy findings were predominantly necroulcerative-to-necrohemorrhagic gastrointestinal lesions. Less frequent lesions included suffusive hemorrhages of serosal surfaces of abdominal viscera, and lymphoid necrosis in gut-associated lymphoid tissues. All of the 6 bighorn sheep that died were positive on real-time PCR (rtPCR) for bovine viral diarrhea virus (BVDV) in multiple tissues. Seroconversion to BVDV-1 and immunohistochemistry for BVDV in affected tissues confirmed rtPCR results. Next-generation sequencing confirmed a match between the infecting strain of BVDV-1b and the contaminated vaccine.


Assuntos
Vírus Bluetongue/imunologia , Bluetongue/prevenção & controle , Doença das Mucosas por Vírus da Diarreia Viral Bovina/diagnóstico , Vírus da Diarreia Viral Bovina/isolamento & purificação , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/etiologia , Bovinos , Colorado , Vírus da Diarreia Viral Bovina/genética , Contaminação de Medicamentos , Feminino , Masculino , Filogenia , Carneiro da Montanha , Vacinação/efeitos adversos , Vacinação/veterinária
16.
Lancet ; 392(10165): 2718-2727, 2019 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30409443

RESUMO

BACKGROUND: Chikungunya fever is an emerging viral disease and substantial threat to public health. We aimed to assess the safety, tolerability, and immunogenicity of a live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK). METHODS: In this double-blind, randomised, placebo-controlled and active-controlled phase 2 trial, we enrolled healthy volunteers aged 18-55 years at four study sites in Austria and Germany. Participants were randomly assigned to receive intramuscular injections with MV-CHIK (5 × 104 or 5 × 105 50% tissue culture infectious dose), control vaccine, or measles prime and MV-CHIK, in two different administration regimens. Randomisation was done by use of three-digit randomisation codes in envelopes provided by a data management service. The participants and investigators were masked to treatment assignment, which was maintained by use of sterile saline as a placebo injection. The primary endpoint was immunogenicity, defined as the presence of neutralising antibodies against chikungunya virus, at day 56, which is 28 days after one or two immunisations. The primary endpoint was assessed in all participants who completed the study without major protocol deviations (per-protocol population) and in all randomised participants who received at least one study treatment (modified intention-to-treat population). The safety analysis included all participants who received at least one study treatment. This trial is registered with ClinicalTrials.gov (NCT02861586) and EudraCT (2015-004037-26) and is completed. FINDINGS: Between Aug 17, 2016, and May 31, 2017, we randomly assigned 263 participants to receive control vaccine (n=34), MV-CHIK (n=195), or measles prime and MV-CHIK (n=34). 247 participants were included in the per-protocol population. Neutralising antibodies against chikungunya virus were detected in all MV-CHIK treatment groups after one or two immunisations, with geometric mean titres ranging from 12·87 (95% CI 8·75-18·93) to 174·80 (119·10-256·50) and seroconversion rates ranging from 50·0% to 95·9% depending on the dose and administration schedule. Adverse events were similar between groups, with solicited adverse events reported in 168 (73%) of 229 participants assigned to MV-CHIK and 24 (71%) of 34 assigned to control vaccine (p=0·84) and unsolicited adverse events in 116 (51%) participants assigned to MV-CHIK and 17 (50%) assigned to control vaccine (p=1·00). No serious adverse events related to the vaccine were reported. INTERPRETATION: MV-CHIK showed excellent safety and tolerability and good immunogenicity, independent of pre-existing immunity against the vector. MV-CHIK is a promising candidate vaccine for the prevention of chikungunya fever, an emerging disease of global concern. FUNDING: Themis.


Assuntos
Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Pessoa de Meia-Idade , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
17.
J Am Anim Hosp Assoc ; 55(1): 29-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30427712

RESUMO

This study described the rate of vaccine reactions in a population of dogs receiving vaccines after diagnosis of primary immune-mediated hemolytic anemia (IMHA). A secondary objective was to describe the time elapsed between vaccination and initial diagnosis of IMHA. A medical record search identified cases meeting criteria for primary IMHA. Owners and referring veterinarians were surveyed regarding vaccination of the dog following diagnosis. Referring veterinarians were surveyed regarding vaccination prior to diagnosis of IMHA. A completed survey was returned in 44 cases. Twenty-two dogs received vaccinations after diagnosis, and 22 dogs did not. The median time elapsed between vaccination and initial diagnosis was 280 days. No dog was vaccinated within 30 days of diagnosis. Two of the following possible reactions were noted out of 22 dogs vaccinated: vomiting and urticarial eruption in a dog administered a rabies and canine distemper vaccine, and recurrent anemia in a dog administered a rabies vaccine. The rate of vaccine reactions was higher than previously reported, although the time period evaluated was longer than in previous studies. The relationship between initial vaccination and development of IMHA, and between vaccination and vaccine reaction, in this population is uncertain and may reflect coincidence or differences in susceptibility.


Assuntos
Anemia Hemolítica/veterinária , Cinomose/prevenção & controle , Doenças do Cão/prevenção & controle , Raiva/veterinária , Vacinação/veterinária , Vacinas Virais/efeitos adversos , Anemia Hemolítica/imunologia , Animais , Doenças do Cão/imunologia , Cães , Raiva/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Vacinação/efeitos adversos
18.
Drug Des Devel Ther ; 12: 4195-4206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30573950

RESUMO

The unprecedented epidemic spread of chikungunya worldwide illustrates the critical need for potent vaccines and therapeutic interventions. The morbidity and mortality associated with this arboviral infection has become a major public health problem in many countries across different continents. Increasing public-private partnerships have opened new avenues in research and development of vaccines. This review mainly focuses on the recent advances in patented approaches for chikungunya vaccine development and the forthcoming challenges.


Assuntos
Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Desenvolvimento de Medicamentos/métodos , Epidemias/prevenção & controle , Vacinas Virais/administração & dosagem , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Ensaios Clínicos como Assunto , Interações Hospedeiro-Patógeno , Humanos , Resultado do Tratamento , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
19.
Front Immunol ; 9: 2884, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574152

RESUMO

A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5-10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.


Assuntos
Animais Recém-Nascidos/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Mastite/imunologia , Pancitopenia/imunologia , Vacinas Virais/efeitos adversos , Criação de Animais Domésticos , Animais , Animais Recém-Nascidos/sangue , Antígenos Virais/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Colostro/imunologia , Colostro/metabolismo , Vírus da Diarreia Viral Bovina/imunologia , Feminino , Incidência , Isoanticorpos/imunologia , Isoanticorpos/metabolismo , Isoantígenos/imunologia , Linfócitos , Mastite/epidemiologia , Pancitopenia/mortalidade , Pancitopenia/veterinária , Fenótipo , Gravidez , Estudos Retrospectivos , Vacinação/efeitos adversos , Vacinas Virais/administração & dosagem
20.
PLoS One ; 13(11): e0206838, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30496299

RESUMO

BACKGROUND: We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. METHODS: Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. RESULTS: Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. CONCLUSION: Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , Imunogenicidade da Vacina , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/genética , Administração Cutânea , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Eletroporação , Feminino , Glucosídeos/imunologia , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Voluntários Saudáveis , Humanos , Imunização Secundária/métodos , Lipídeo A/imunologia , Masculino , Moçambique , Tanzânia , Vacinação/métodos , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Vacinas de DNA/genética , Vírus Vaccinia/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/genética , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
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