RESUMO
In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications.
Assuntos
Vacinas contra Dengue/administração & dosagem , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Administração Cutânea , Animais , Anticorpos Antivirais/sangue , Dengue/sangue , Dengue/imunologia , Dengue/virologia , Vacinas contra Dengue/genética , Vacinas contra Dengue/imunologia , Vírus da Dengue/genética , Humanos , Imunização , Imunoglobulina G/sangue , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of the Flaviviridae family firstly isolated from sentinels Rhesus sp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spread Aedes aegypti mosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far.(AU)
Assuntos
Artrogripose , Aedes , Zika virus , Microcefalia , Modelos TeóricosRESUMO
Abstract Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of the Flaviviridae family firstly isolated from sentinels Rhesus sp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spread Aedes aegypti mosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far.