Abstract
The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.
Highlights
Dengue has been registered and associated with human beings for more than a thousand years [1]
The physical status of actual virus morphology in acute dengue plasma has been reported; a form of dengue virus (DENV) vesicles in vivo rather than classical dengue virions was obtained from Vero cell culture [44], and these in vivo viral particles are not easy to neutralize by human antibodies [45]
The results demonstrated that a unique viral morphology, similar to that of plasma of acute dengue patients, was observed (Figure 1A) in plasma of healthy asymptomatic subject who has very high dengue viral titer
Summary
Dengue has been registered and associated with human beings for more than a thousand years [1]. Various clinical symptoms including asymptomatic, mild undifferentiated fever, classical dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). If the findings are substantiated in other parts of the geographical locales, one of the critical questions is what can be done if asymptomatic individuals carrying high infectious DENV are identified? The criteria and guidelines for the diagnosis of DF and DHF/DSS have been well-established by WHO since 1997, revised by WHO South-East Asia Regional Office (SEARO) in 2011 [13]. Multiple molecular mechanisms accounting for the dynamic clinical presentations of disease seen by physicians may contribute to the pathogenic cause of DHF/DSS [26,27]
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