ABSTRACT

Introduction

The induction of a functional immune response against the four viral serotypes is one of the premises for an effective vaccine against Dengue virus. This is challenging since the immunization with four antigens leads to immunologic phenomena such as antigen interference, immuno-dominance, and tolerance. Moreover, the four serotypes have intrinsic features that impact the outcome after the immunization with a tetravalent formulation.

Areas covered

This work reviews the main studies evidencing the differences between Dengue virus 4 and the rest of the serotypes. We address some peculiarities of this virus and discuss which factors could explain the heterogeneous response achieved after the immune evaluation of tetravalent formulations.

Expert opinion

The low immunogenicity associated with serotype 4 could slow down the development of a vaccine against Dengue virus. Achieving similar levels of neutralizing antibodies against the four serotypes has been the goal of many vaccine developers. However, this does not need to be seen as a mandatory dogma. High levels of efficacy against Dengue virus 4 could be reached even if it shows the lowest neutralizing antibody titers among the viral complex. Studies on the efficacy of vaccines, currently in phase III clinical trials, should shed light on this concern in the near future.

中文翻译：

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登革热病毒4：家庭的“败类”？

摘要

介绍

诱导针对四种病毒血清型的功能性免疫应答是抗登革热病毒有效疫苗的前提之一。这是具有挑战性的，因为用四种抗原免疫会导致免疫学现象，例如抗原干扰，免疫优势和耐受性。此外，四种血清型具有内在特征，这些固有特征会影响四价制剂免疫后的结果。

覆盖区域

这项工作回顾了主要研究，以证明登革热病毒4与其余血清型之间的差异。我们解决了该病毒的一些特殊问题，并讨论了哪些因素可以解释四价制剂的免疫评估后实现的异质性反应。

专家意见

与血清型4相关的低免疫原性可能减慢针对登革热病毒的疫苗的开发。实现相似水平的针对四种血清型的中和抗体已成为许多疫苗开发人员的目标。但是，这不必视为强制性教条。即使它在病毒复合物中显示出最低的中和抗体效价，也可以达到高水平的抗登革热病毒4的功效。目前正在进行III期临床试验的疫苗功效研究应在不久的将来阐明这一问题。