Working towards dengue as a vaccine-preventable disease: challenges and opportunities

ABSTRACT

Introduction: Dengue is an emerging viral disease that affects the human population around the globe. Recent advancements in dengue virus research have opened new avenues for the development of vaccines against dengue. The development of a vaccine against dengue is a challenging task because any of the four serotypes of dengue viruses can cause disease. The development of a dengue vaccine aims to provide balanced protection against all the serotypes. Several dengue vaccine candidates are in the developmental stages such as inactivated, live attenuated, recombinant subunit, and plasmid DNA vaccines.

Area covered: The authors provide an overview of the progress made in the development of much needed dengue vaccines. The authors include their expert opinion and their perspectives for future developments.

Expert opinion: Human trials of a live attenuated tetravalent chimeric vaccine have clearly demonstrated its potential as a dengue vaccine. Other vaccine candidate molecules such as DENVax, a recombinant chimeric vaccine andTetraVax, are at different stages of development at this time. The authors believe that the novel strategies for testing and improving the immune response of vaccine candidates in humans will eventually lead to the development of a successful dengue vaccine in future.

KEYWORDS:

• Dengue virus
• antibody dependent enhancement
• live attenuated vaccine
• subunit vaccine
• inactivated tetravalent vaccine
• DNA vaccine

Article highlights

• The dengue vaccine field has constantly been experiencing new challenges in addition to the usual ones including the necessity to design tetravalent formulations and the risk that incomplete immunization may lead to enhanced disease severity.

• Phase III trials with the Sanofi Pasteur dengue vaccine candidate have called for a detailed understanding of the immunological processes responsible for protection against dengue virus infection, thus, necessitating alternative marker for protection efficacy of vaccine candidates.

• The immune response of both CD4+ and CD8+T cells against dengue has an important role in the protection against dengue virus.

• Presently, most of the advanced vaccine candidates consist of attenuated or inactivated dengue virus, yet subunit vaccine candidates are in the pipeline as a second generation vaccine.

• Various innovative strategies are being evolved consistently to increase the immunogenicity of subunit vaccine candidates for dengue.

• The identification of novel protective epitopes on the dengue virus will lead to the development of newer and more efficacious dengue subunit vaccines in the future.

This box summarizes key points contained in the article.

Acknowledgments

The authors are thankful to the Director, DRDE, Gwalior for his keen interest and support in this study. The authors had this manuscript language edited by ManuscriptEdit by Reseapro.

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.

Additional information

Funding

The authors are supported by the Defence Research and Development Organization (of the Ministry of Defence of the Government of India).