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1.
Vaccine ; 39(36): 5173-5186, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34353682

RESUMO

Zika virus (ZIKV) caused over two million human infections in more than 80 countries around 2015-2016. Current vaccines under development are mostly focused on inducing antibodies that despite capable of inhibiting the virus, may have the potential to trigger antibody dependent enhancement (ADE). T cell vaccines that do not induce antibodies targeting viral surface will unlikely cause ADE, but be capable of potentiating the effectiveness of an antibody-inducing vaccine. To develop such a protective T cell vaccine, we first examined the repertoire of antigen-specific T cells in immunocompetent mice that have been transiently infected by ZIKV. Through epitope mapping using 427 overlapping peptides spanning the entire length of ZIKV polyprotein, we discovered 27 immunodominant epitopes scattered throughout the virus on C, E, NS1-NS5 proteins. Among them, 8 were confirmed as CD4+ T cell epitopes, and 16 as CD8+ T cell epitopes, while 3 for both T cell subsets. From these 27 newly identified epitopes, the top 10 epitopes were selected to formulate three T cell vaccines comprised of either CD4+ T cell epitopes, or CD8+ T cell epitopes, or a mixture of both. Immunization with these T cell epitopes induced T cell-mediated cytotoxicity and cytokine production, and conferred varying degrees of protection against ZIKV challenge. Moreover, these new T cell vaccines also improved the protective efficacy of a neutralizing antibody-inducing recombinant E80 protein vaccine. Together, our results provided additional evidence in support of the protective role of ZIKV-specific CD4+ and CD8+ T cells, and laid foundation for future development of T cell vaccines for ZIKV.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Mapeamento de Epitopos , Epitopos de Linfócito T , Epitopos Imunodominantes , Camundongos , Vacinas Sintéticas , Infecção por Zika virus/prevenção & controle
2.
BMC Health Serv Res ; 21(1): 866, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429111

RESUMO

BACKGROUND: Effective control of emerging mosquito-borne viral diseases such as dengue, chikungunya, and Zika requires, amongst other things, a functional healthcare system, ready and capable of timely detection and prompt response to incipient epidemics. We assessed the readiness of Zanzibar health facilities and districts for early detection and management of mosquito-borne viral disease outbreaks. METHODS: A cross-sectional study involving all 10 District Health Management Teams and 45 randomly selected public and private health facilities in Zanzibar was conducted using a mixed-methods approach including observations, document review, and structured interviews with health facility in-charges and District Health Management Team members. RESULTS: The readiness of the Zanzibar healthcare system for timely detection, management, and control of dengue and other mosquito-borne viral disease outbreaks was critically low. The majority of health facilities and districts lacked the necessary requirements including standard guidelines, trained staff, real-time data capture, analysis and reporting systems, as well as laboratory diagnostic capacity. In addition, health education programmes for creating public awareness and Aedes mosquito surveillance and control activities were non-existent. CONCLUSIONS: The Zanzibar healthcare system has limited readiness for management, and control of mosquito-borne viral diseases. In light of impending epidemics, the critical shortage of skilled human resource, lack of guidelines, lack of effective disease and vector surveillance and control measures as well as lack of laboratory capacity at all levels of health facilities require urgent attention across the Zanzibar archipelago.


Assuntos
Aedes , Epidemias , Viroses , Infecção por Zika virus , Zika virus , Animais , Estudos Transversais , Atenção à Saúde , Humanos , Mosquitos Vetores , Tanzânia/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
3.
Artigo em Inglês | MEDLINE | ID: mdl-34406289

RESUMO

Infections caused by arboviruses that have mostly impacted the Brazilian morbidity and mortality are caused by the same vector, Aedes aegypti. Preventive actions related to the vector are the most effective strategies in the prevention and control of these diseases. This study aimed to associate the knowledge on the vector that transmits dengue, Zika and chikungunya with the sociodemographic and behavioral preventive practices towards Aedes aegypti in the municipality of Tangara da Serra, Mato Grosso State, in the Brazilian Legal Amazon. A probabilistic urban population sampling was obtained by clusters: census sectors and households. The sample size calculation considered 10% of loss and a 1.5 design effect. This is a cross-sectional research carried out through a household survey in February and March 2018. There were 583 participants. The study variables were knowledge on the vector, sociodemographic characteristics and preventive practices related to the vector. The statistical analysis was based on a bivariate analysis and Poisson multiple regressions. Inadequate or insufficient knowledge on the vector Aedes aegypti remained associated with education in the categories illiterate (p<0.001) and 8 years of study or less (p<0.001), in addition to not adopting practices of capping and cleaning the water tank (p=0.002) and not using insecticides at home (p=0.007). It is concluded that there is a need for health communication actions that consider characteristics the population, especially the level of education and previous knowledge on the vector, allowing a dialogical approach and enabling the community participation in preventive practices and control of the vector Aedes aegypti .


Assuntos
Aedes , Dengue , Infecção por Zika virus , Zika virus , Animais , Estudos Transversais , Dengue/prevenção & controle , Humanos , Controle de Mosquitos , Mosquitos Vetores , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
4.
BMC Public Health ; 21(1): 1362, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243740

RESUMO

BACKGROUND: The outbreak of Zika virus in Brazil in 2015 followed the arrival of chikungunya in 2014 and a long history of dengue circulation. Vital to the response to these outbreaks of mosquito-borne pathogens has been the dissemination of public health messages, including those promoted through risk communication posters. This study explores the content of a sample of posters circulated in Brazil towards the end of the Zika epidemic in 2017 and analyses their potential effectiveness in inducing behaviour change. METHODS: A content analysis was performed on 37 posters produced in Brazil to address outbreaks of mosquito-borne pathogens. The six variables of the Health Belief Model were used to assess the potential effectiveness of the posters to induce behaviour change. RESULTS: Three overarching key messages emerged from the posters. These included (i) the arboviruses and their outcomes, (ii) a battle against the mosquito, and (iii) a responsibility to protect and prevent. Among the six variables utilised through the Health Belief Model, cues to action were most commonly featured, whilst the perceived benefits of engaging in behaviours to prevent arbovirus transmission were the least commonly featured. CONCLUSIONS: The posters largely focused on mosquito-borne transmission and the need to eliminate breeding sites, and neglected the risk of the sexual and congenital transmission of Zika and the importance of alternative preventive actions. This, we argue, may have limited the potential effectiveness of these posters to induce behaviour change.


Assuntos
Aedes , Arbovírus , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Animais , Brasil/epidemiologia , Dengue/epidemiologia , Dengue/prevenção & controle , Humanos , Mosquitos Vetores , Saúde Pública , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
5.
Vaccine ; 39(33): 4700-4704, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34229891

RESUMO

Maternal immunization is key to protecting maternal and newborn health. We interviewed pregnant women in Brazil to identify barriers to and enablers of maternal immunization in the country. In-depth interviews and focus groups were conducted in Brazil with 60 pregnant women from São Paulo and Rio de Janeiro at different stages of their pregnancies. Participants were encouraged to discuss views on safety, efficacy and importance of maternal vaccines, access to vaccines, interactions with healthcare professionals, and sources of information on vaccine-related matters. There was generally a positive regard for maternal immunization among the interviewed women, many of whom associated vaccination with protection of their unborn child. The interviewees cited several reasons for adherence to immunization guidelines, including recommendations from healthcare professionals, targeted communication campaigns, and active use of a vaccination card or booklet. There were no reported barriers for maternal vaccines. Some women using private healthcare services reported not having been asked about vaccines at check-ups, which could adversely affect vaccination rates. A rumour that vaccines caused microcephaly which emerged during the Zika outbreak was the most commonly cited reason for choosing not to vaccinate among the interviewees. This study identified important vaccine confidence builders. Many of the interviewees critically reflected upon information received, placing themselves as the decision makers over their health choices. A prominent barrier to maternal immunization was a rumour linking vaccines to microcephaly. To the best of our knowledge, this has not been previously reported in the literature and requires further investigation into the extent of this issue and how it can be mitigated.


Assuntos
Vacinas , Infecção por Zika virus , Zika virus , Brasil , Criança , Surtos de Doenças , Feminino , Humanos , Recém-Nascido , Gravidez , Vacinação , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
6.
Nat Immunol ; 22(8): 958-968, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34267374

RESUMO

Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. Cross-reactive antibodies targeting the conserved fusion loop epitope (FLE) are known as the main sources of ADE. We design ZIKV immunogens engineered to change the FLE conformation but preserve neutralizing epitopes. Single vaccination conferred sterilizing immunity against ZIKV without ADE of DENV-serotype 1-4 infections and abrogated maternal-neonatal transmission in mice. Unlike the wild-type-based vaccine inducing predominately cross-reactive ADE-prone antibodies, B cell profiling revealed that the engineered vaccines switched immunodominance to dispersed patterns without DENV enhancement. The crystal structure of the engineered immunogen showed the dimeric conformation of the envelope protein with FLE disruption. We provide vaccine candidates that will prevent both ZIKV infection and infection-/vaccination-induced DENV ADE.


Assuntos
Anticorpos Facilitadores/imunologia , Antígenos Virais/imunologia , Reações Cruzadas/imunologia , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Zika virus/imunologia , Aedes , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Chlorocebus aethiops , Cricetinae , Vírus da Dengue/imunologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Vacinação , Células Vero , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle
7.
Urologe A ; 60(9): 1150-1158, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34228144

RESUMO

INTRODUCTION: The COVID (coronavirus disease 2019) pandemic has shown impressively that infectious diseases can have an enormous impact on the healthcare system and beyond. In the specialty of urology, patients present in daily practice with viral infections that are associated with numerous diseases. METHODOLOGY: The aim of this review is to describe viral infections relevant for urology, and in particular to emphasize vaccination prevention. A selective literature search was carried out on the subjects of "COVID and urology", "urogenital viral infections", "viral urological infections in transplant medicine", and "vaccination prevention of viral diseases". RESULTS: Coronaviruses have already caused two local epidemics: SARS (severe acute respiratory syndrome) epidemic and MERS (Middle East respiratory syndrome) epidemic. The fact that the SARS-CoV­2 (SARS coronavirus 2) disease is contagious even without symptoms has essentially led to the rapid spread and global pandemic. A large number of viruses, which can also induce viremia, have been detected in the ejaculate and are thus associated with a possible urogenital infection. These include the mumps virus, Coxsackie viruses or enteroviruses, among others. It has also been shown that a Zika virus infection can also be sexually transmitted via the sperm as a carrier. Viruses therefore also play an important role in reproduction. When performing kidney transplants, urologists are often confronted with viral infections. The most effective weapon against viruses is prevention by vaccination. CONCLUSION: In terms of ethiopathogenesis, the genitourinary tract is most often affected by viruses, in the context of viremia or through reactivation due to immunosuppression. Immunomodulation and vaccination prophylaxis play a leading role in therapy.


Assuntos
COVID-19 , Urologia , Viroses , Infecção por Zika virus , Zika virus , Humanos , Pandemias , SARS-CoV-2 , Viroses/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
8.
J Glob Health ; 11: 05012, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34221359

RESUMO

Background: Strategic planning is critical for successful pandemic management. This study aimed to identify and review the scope and analytic depth of situation analyses conducted to understand their utility, and capture the documented macro-level factors impacting pandemic management. Methods: To synthesise this disparate body of literature, we adopted a two-step search and review process. A systematic search of the literature was conducted to identify all studies since 2000, that have 1) employed a situation analysis; and 2) examined contextual factors influencing pandemic management. The included studies are analysed using a seven-domain systems approach from the discipline of strategic management. Results: Nineteen studies were included in the final review ranging from single country (6) to regional, multi-country studies (13). Fourteen studies had a single disease focus, with 5 studies evaluating responses to one or more of COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Influenza A (H1N1), Ebola virus disease, and Zika virus disease pandemics. Six studies examined a single domain from political, economic, sociological, technological, ecological or wider industry (PESTELI), 5 studies examined two to four domains, and 8 studies examined five or more domains. Methods employed were predominantly literature reviews. The recommendations focus predominantly on addressing inhibitors in the sociological and technological domains with few recommendations articulated in the political domain. Overall, the legislative domain is least represented. Conclusions: Ex-post analysis using the seven-domain strategic management framework provides further opportunities for a planned systematic response to pandemics which remains critical as the current COVID-19 pandemic evolves.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , Influenza Humana , Pandemias/prevenção & controle , Infecção por Zika virus , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , SARS-CoV-2 , Zika virus , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
9.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-48260

RESUMO

Cientistas do Instituto de Química da USP e da Fiocruz do Rio de Janeiro e da Bahia identificaram consideráveis alterações lipídicas no plasma de recém-nascidos com exposição pré-natal ao vírus da zika.


Assuntos
Microcefalia/diagnóstico , Microcefalia/prevenção & controle , Zika virus , Recém-Nascido/líquido cefalorraquidiano , Infecção por Zika virus/prevenção & controle , Insuficiência Placentária/diagnóstico
10.
Biochim Biophys Acta Mol Basis Dis ; 1867(10): 166198, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34118406

RESUMO

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal­neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.


Assuntos
Anormalidades Congênitas/etiologia , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Viroses/complicações , Animais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/transmissão , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/prevenção & controle , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/transmissão , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Resultado da Gravidez , SARS-CoV-2/isolamento & purificação , Viroses/diagnóstico , Viroses/prevenção & controle , Viroses/transmissão , Zika virus/isolamento & purificação , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
11.
BMJ Glob Health ; 6(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34117012

RESUMO

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.


Assuntos
Epidemias , Viroses , Infecção por Zika virus , Zika virus , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Viroses/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
12.
Salud Publica Mex ; 63(3 May-Jun): 452-458, 2021 May 03.
Artigo em Espanhol | MEDLINE | ID: mdl-34098620

RESUMO

Objetivo. Describir y analizar el gasto de la Secretaría de Salud asociado con iniciativas de comunicación social de las campañas de prevención de enfermedades transmitidas por vectores (Zika, chikunguña y dengue) y la evaluación de impacto o resultados. Material y métodos. La in-formación se obtuvo de 690 contratos de prestación de servicios de comunicación social (2015-2017), asociados con dos declaraciones de emergencia epidemiológica (EE- 2-2015 y EE-1-2016). Resultados. Se concluye una débil evaluación de impacto del gasto público. No existe evidencia suficiente que demuestre la correspondencia del gasto en comunicación social con la efectividad y cumplimiento de las campañas. Conclusiones. Los hallazgos permiten definir recomendaciones para vigilar, transparentar y hacer más eficiente el gasto público. Existe información pública sobre el gasto; sin embargo, es necesario garantizar mecanismos de transparencia, trazabilidad de contratos y evaluación de impacto de las campañas.


Assuntos
Comunicação em Saúde , Promoção da Saúde , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/prevenção & controle , Dengue/epidemiologia , Dengue/prevenção & controle , Comunicação em Saúde/economia , Promoção da Saúde/economia , Humanos , México/epidemiologia , Avaliação de Programas e Projetos de Saúde , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
14.
Am J Prev Med ; 61(3): e149-e155, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33952412

RESUMO

INTRODUCTION: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors. METHODS: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status. RESULTS: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55). CONCLUSIONS: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years.


Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Adulto , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Gravidez não Planejada , Porto Rico/epidemiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle
16.
Rev Soc Bras Med Trop ; 54(suppl 1): e2020609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008724

RESUMO

This article addresses the vector, sexual and vertical transmissions of the Zika virus, a topic covered in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Although in Brazil Zika virus is transmitted more predominantly by Aedes aegypti, the vertical and sexual transmission routes are of significant importance for reproductive health. Sexual transmission demands specific prophylactic interventions, including the use of male or female condoms, especially among couples in a risk situation and planning pregnancy. Vertical transmission is linked to severe structural abnormalities of the central nervous system, and there is still no vaccine or known pharmacological resources that can prevent it. As the disease is predominantly asymptomatic, failure to comply with the basic principles of care and guidelines associated with the spread of the infection transcends the severity of the disease's symptoms. Although in Brazil Zika virus is predominantly transmitted by the Aedes aegypti mosquito, vertical and sexual transmission routes are important for reproductive health. Vertical transmission causes severe central nervous system structural abnormalities.


Assuntos
Aedes , Doenças Sexualmente Transmissíveis , Infecção por Zika virus , Zika virus , Animais , Brasil , Feminino , Humanos , Masculino , Mosquitos Vetores , Gravidez , Infecção por Zika virus/prevenção & controle
17.
Lancet Infect Dis ; 21(9): 1282-1292, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34019802

RESUMO

BACKGROUND: Zika virus, a flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is associated with cases of congenital malformations and neurological complications. Absence of specific treatment makes a prophylactic Zika virus vaccine an unmet medical need. We assessed safety and immunogenicity of three doses of a purified, inactivated, Zika virus vaccine candidate in healthy flavivirus-naive and flavivirus-primed adults. METHODS: This two-part, multicentre, observer-blind, randomised, placebo-controlled, phase 1 trial was done at seven medical clinics in the USA and two in Puerto Rico. Eligible participants were healthy adults aged 18-49 years. Participants were randomly assigned (1:1:1:1), using a sponsor-supplied randomisation scheme, to four groups to receive two intramuscular injections, 28 days apart, of saline placebo or TAK-426 containing 2 µg, 5 µg, or 10 µg antigen. Participants, investigators, and vaccine administrating personnel were masked to group assignment. Part 1 of the study assessed flavivirus-naive participants and part 2 assessed flavivirus-primed participants. The primary outcomes were safety, tolerability, and immunogenicity based on solicited local reactions and solicited systemic adverse events in the 7 days after each dose; unsolicited adverse events and serious adverse events in the 28 days after each dose; and geometric mean titres (GMTs) of neutralising anti-Zika virus antibodies at 28 days after the second dose. Safety assessments were done in all participants who received at least one dose of vaccine. Immunogenicity assessments were in the per-protocol set, comprising all participants who received at least one dose of vaccine and provided valid serology results at baseline and at least one post-vaccination timepoint, with no major protocol violations. The trial is ongoing and is registered at ClinicalTrials.gov (NCT03343626). FINDINGS: Between Nov 13, 2017, and Oct 24, 2018, 894 volunteers were screened and 271 enrolled (125 flavivirus-naive and 146 flavivirus-primed participants). All TAK-426 doses were well tolerated with no deaths, no vaccine-related serious adverse events, and similar rates of mainly mild to moderate adverse events. TAK-426 elicited dose-dependent increases in antibody GMTs in both flavivirus-naive and flavivirus-primed participants. 28 days after dose 2, plaque-reduction neutralisation test GMTs in flavivirus-naive participants were 1130 (95% CI 749-1703) in the 2 µg TAK-426 group, 1992 (1401-2833) in the 5 µg TAK-426 group, and 3690 (2677-5086) in the 10 µg TAK-426 group. In pairwise comparisons, responses after two vaccinations in the 10 µg group were significantly greater than in the 2 µg group (GMT ratio 3·27 [95% CI 1·98-5·39], p<0·0001) and the 5 µg group (GMT ratio 1·85 [1·15-2·98], p=0·012). INTERPRETATION: TAK-426 was well tolerated, with an acceptable safety profile, and was immunogenic in both flavivirus-naive and flavivirus-primed adults. Based on the safety and immunogenicity profiles of all TAK-426 doses assessed, the 10 µg TAK-426 dose was selected for further clinical development. FUNDING: Takeda Vaccines and the US Biomedical Advanced Research and Development Authority. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.


Assuntos
Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Formação de Anticorpos , Bases de Dados Factuais , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
18.
Rev Esp Salud Publica ; 952021 May 10.
Artigo em Espanhol | MEDLINE | ID: mdl-33967267

RESUMO

OBJECTIVE: Environmental management of imported arboviruses such as dengue (DENV), Zika (ZIKV) or Chikungunya (CHIKV) is a task of great significance for Public Health since the arrival and establishment of the competent vector Aedes albopictus (Asian tiger mosquito) in numerous cities of our country. There are recent examples of autochthonous transmission of some of these arboviruses in Spain probably linked to undetected and / or unmanaged imported cases. METHODS: Vector management interventions were carried out in the city of Valencia (Spain) by the Health Service of the Valencia City Council between 2016 and 2018. These actions took place within the framework of a coordination protocol established with the Health authorities of the Valencia regional government. RESULTS: A total of 21 arbovirus cases were reported and led to entomological surveillance and vector control interventions in the city of Valencia: 8 DENV, 7 CHIKV and 6 ZIKV. In 8 of these 21 cases (38%) the presence of Ae. Albopictus was detected within the risk zones established for each case. CONCLUSIONS: Vector surveillance and control strategies associated with imported cases of arboviruses, provide accurate information on the environmental risks of amplification of these viruses and also allow reducing these risks through population control of vectors. Due to the short duration of the viremic phases, these interventions should be carried out as quickly as possible in order to reduce the hypothetical contact between the infected person and vector as much as possible.


Assuntos
Aedes/virologia , Febre de Chikungunya/prevenção & controle , Dengue/prevenção & controle , Controle de Mosquitos , Mosquitos Vetores/virologia , Infecção por Zika virus/prevenção & controle , Animais , Febre de Chikungunya/epidemiologia , Cidades/epidemiologia , Dengue/epidemiologia , Humanos , Espanha/epidemiologia , Infecção por Zika virus/epidemiologia
19.
J Virol ; 95(14): e0038321, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-33910950

RESUMO

Zika virus (ZIKV) infection during pregnancy has been linked to congenital abnormalities, such as microcephaly in infants. An efficacious vaccine is desirable for preventing the potential recurrence of ZIKV epidemic. Here, we report the generation of an attenuated ZIKV (rGZ02a) that has sharply decreased virulence in mice but grows to high titers in Vero cells, a widely approved cell line for manufacturing human vaccines. Compared to the wild-type ZIKV (GZ02) and a plasmid-launched rGZ02p, rGZ02a has 3 unique amino acid alterations in the envelope (E, S304F), nonstructural protein 1 (NS1, R103K), and NS5 (W637R). rGZ02a is more sensitive to type I interferon than GZ02 and rGZ02p, and causes no severe neurological disorders in either wild-type neonatal C57BL/6 mice or type I interferon receptor knockout (Ifnar1-/-) C57BL/6 mice. Immunization with rGZ02a elicits robust inhibitory antibody responses with a certain long-term durability. Neonates born to the immunized dams are effectively protected against ZIKV-caused neurological disorders and brain damage. rGZ02a as a booster vaccine greatly improves the protective immunity primed by Ad2-prME, an adenovirus-vectored vaccine expressing ZIKV prM and E proteins. Our results illustrate that rGZ02a-induced maternal immunity can be transferred to the neonates and confer effective protection. Hence, rGZ02a may be developed as an alternative live-attenuated vaccine and warrants further evaluation. IMPORTANCE Zika virus (ZIKV), a mosquito-borne flavivirus that has caused global outbreaks since 2013, is associated with severe neurological disorders, such as Guillian-Barré syndrome in adults and microcephaly in infants. The ZIKV epidemic has gradually subsided, but a safe and effective vaccine is still desirable to prevent its potential recurrence, especially in countries of endemicity with competent mosquito vectors. Here, we describe a novel live-attenuated ZIKV, rGZ02a, that carries 3 unique amino acid alterations compared to the wild-type GZ02 and a plasmid-launched rGZ02p. The growth capacity of rGZ02a is comparable to GZ02 in Vero cells, but the pathogenicity is significantly attenuated in two mice models. Immunization with rGZ02a elicits robust inhibitory antibody responses in the dams and effectively protects their offspring against ZIKV disease. Importantly, in a heterologous prime-boost regimen, rGZ02a effectively boosts the protective immunity primed by an adenovirus-vectored vaccine. Thus, rGZ02a is a promising candidate for a live-attenuated ZIKV vaccine.


Assuntos
Imunogenicidade da Vacina , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adenoviridae/genética , Animais , Animais Recém-Nascidos , Chlorocebus aethiops , Feminino , Vetores Genéticos , Imunização Secundária , Interferon Tipo I/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Células Vero , Proteínas Virais/genética , Zika virus/genética , Infecção por Zika virus/imunologia
20.
Viruses ; 13(4)2021 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920474

RESUMO

Most alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since it is not infectious for vertebrates and therefore provides a highly advantageous safety profile. Here, we investigated the feasibility of versatile EILV-based expression vectors. By replacing the structural genes of EILV with those of other alphaviruses, we generated seven different chimeras. These chimeras were readily rescued in the original mosquito cells and were able to reach high titers, suggesting that EILV is capable of packaging the structural proteins of different lineages. We also explored the ability of EILV to express authentic antigens via double subgenomic (SG) RNA vectors. Four foreign genetic materials of varied length were introduced into the EILV genome, and the expressed heterologous genetic materials were readily detected in the infected cells. By inserting an additional SG promoter into the chimera genome containing the structural genes of Chikungunya virus (CHIKV), we developed a bivalent vaccine candidate against CHIKV and Zika virus. These data demonstrate the outstanding compatibility of the EILV genome. The produced recombinants can be applied to vaccine and diagnostic tool development, but more investigations are required.


Assuntos
Alphavirus/genética , Culicidae/virologia , Vetores Genéticos , Genoma Viral , Vacinas Virais/genética , Animais , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/genética , Chlorocebus aethiops , Culicidae/citologia , Mosquitos Vetores/virologia , Regiões Promotoras Genéticas , Vacinas Sintéticas/genética , Células Vero , Replicação Viral , Zika virus/genética , Infecção por Zika virus/prevenção & controle
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