Dengue virus 4: the ‘black sheep’ of the family?

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.

KEYWORDS:

• Dengue
• serotype
• vaccine
• DENV-4
• dengue virus-4

Article highlights

• Dengue vaccine must induce an effective and long-lasting immune response against the four viral serotypes.

• Intrinsic features of Dengue virus serotype 4 impact the outcome of the immunization with a tetravalent formulation.

• The comparison between the titers of neutralizing antibodies should be carefully performed since different techniques, sera and virus dilutions, cell lines and their membrane receptors influence the results achieved.

Acknowledgments

The author thanks Dr. Eduardo Martínez-Montes (Cuban Neuroscience Center) for his critical reading of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work was supported by the Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.