An update on dengue vaccine development, challenges, and future perspectives

ABSTRACT

Introduction

From both a public health and economic perspective, vaccination is arguably the most effective approach to combat endemic and pandemic infectious diseases. Dengue affects more than 100 countries in the tropical and subtropical world, with 100–400 million infections every year. In the wake of the recent setback faced by Dengvaxia, the only FDA-approved dengue vaccine, safer and more effective dengue vaccines candidates are moving along the clinical pipeline.

Area covered

This review provides an update of the latest outcomes of dengue vaccine clinical trials. In the light of recent progress made in our understanding of dengue pathogenesis and immune correlates of protection, novel vaccine strategies have emerged with promising second-generation dengue vaccine candidates. Finally, the authors discuss the dengue-specific challenges that remain to be addressed and overcome.

Expert opinion

The authors propose to explore various adjuvants and delivery systems that may help improve the design of safe, effective, and affordable vaccines against dengue. They also challenge the concept of a ‘universal’ dengue vaccine as increasing evidence support that DENV strains have evolved different virulence mechanisms.

KEYWORDS:

• Dengue vaccine candidates
• antibody-dependent enhancement
• T cell responses
• non-structural protein (NS)1
• mRNA vaccines
• immune correlates of protection
• animal and human models of dengue infection

Article highlights

• Dengue remains a major public health concern and economic burden to more than 100 countries in the tropical and subtropical world.

• The suboptimal protective efficacy and safety issues associated with the only FDA-approved dengue vaccine have boosted the pursuit of better dengue vaccine candidates.

• The clinical pipeline is dominated by live attenuated tetravalent formulations.

• T cell responses are being increasingly considered as immune correlates of protection and T-cell mediated protection should be considered in novel vaccination strategies.

• mRNA vaccine approaches boosted under the COVID19 crisis, may benefit the dengue vaccine field.

• The design of a universal dengue vaccine may be difficult to achieve due to the diversity of virulence mechanisms amongst DENV strains.

This box summarizes key points contained in the article.

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.