Lazo Laura
Vaccine Department, Center for Genetic Engineering and Biotechnology Havana , Havana, Cuba.
Expert Rev Vaccines. 2020 Sep;19(9):807-815. doi: 10.1080/14760584.2020.1813578. Epub 2020 Oct 12.
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.
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.
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.
诱导针对四种病毒血清型的功能性免疫反应是有效登革热病毒疫苗的前提之一。这具有挑战性，因为用四种抗原进行免疫会导致抗原干扰、免疫优势和耐受性等免疫现象。此外，这四种血清型具有内在特征，会影响用四价制剂免疫后的结果。
本研究回顾了主要研究，这些研究证明了登革热病毒4型与其他血清型之间的差异。我们阐述了这种病毒的一些特性，并讨论了哪些因素可以解释在对四价制剂进行免疫评估后所获得的异质性反应。
与4型血清型相关的低免疫原性可能会减缓登革热病毒疫苗的研发进程。使针对四种血清型的中和抗体达到相似水平一直是许多疫苗研发者的目标。然而，这不一定非得被视为一条必须遵循的教条。即使登革热病毒4型在病毒复合体中显示出最低的中和抗体滴度，也有可能实现对其的高效防护。目前处于III期临床试验阶段的疫苗疗效研究应会在不久的将来阐明这一问题。
