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  • Review Article
  • Published:

Prospects for a dengue virus vaccine

Nature Reviews Microbiology volume 5, pages 518–528 (2007)Cite this article

Key Points

  • There are four serotypes of dengue virus (DENV) that are maintained in a human–mosquito–human transmission cycle in most of the tropical and subtropical regions of the world. DENV causes more human disease than any other arbovirus.

  • DENV infection can result in a wide range of outcomes from inapparent infection to dengue fever to potentially fatal dengue haemorrhagic fever (DHF) with shock. The prevalence of severe DENV disease is increasing throughout the world.

  • Infection with DENV elicits a strong neutralizing antibody response against the infecting serotype that is believed to induce lifelong protection against only that particular serotype. DENV-specific T cells are also induced by infection and are believed to aid in the resolution of infection.

  • Conversely, the immune response also appears to be a major factor in the pathogenesis of severe dengue disease. The enhanced disease severity observed in patients undergoing a secondary infection with a virus belonging to a different serotype has been associated with the phenomenon of antibody-dependent enhancement (ADE).

  • An ideal vaccine for DENV must be tetravalent because each of the four serotypes are present throughout the world and each can cause disease. The vaccine should induce neutralizing antibody levels comparable with those observed in wild-type virus infection to limit the risk of ADE. Finally, the vaccine should be available at a low cost for the developing world

  • Multiple live attenuated vaccine candidates are presently being evaluated in clinical trials. Clinical safety and strong immunogenicity have been observed for empirically derived vaccine strains and for recombinant viruses using either genetically modified full-length vaccine strains or antigenic chimeric viruses.

  • Inactivated monovalent vaccines and a recombinant subunit vaccine consisting of purified envelope protein are scheduled to be tested in clinical trials soon. Other approaches are being evaluated preclinically.

  • Considerable progress has been made in the development of DENV vaccine candidates in the past few years. One or more of the strategies being currently pursued should be successful in reducing the disease burden caused by this emerging pathogen.

Abstract

The number of cases of severe dengue disease continues to grow in endemic areas of southeast Asia, Central and South America, and other subtropical regions. Children bear the greatest burden of disease, and the development of an effective vaccine remains a global public health priority. A tetravalent vaccine is urgently needed and must be effective against all four dengue virus serotypes, be cost-effective and provide long-term protection. In this Review we discuss the unique immunological concerns in dengue virus vaccine development and the current prospects for the development of an acceptable vaccine, a goal that is likely to be reached in the near future.

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Figure 1: A decade of dengue disease 1995–2005.
Figure 2: Transmission of dengue viruses.
Figure 3: Model for antibody-dependent enhancement of dengue virus replication.

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Acknowledgements

Support for S.S.W., J.E.B., A.P.D. (in part) and B.R.M. is provided by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

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Authors and Affiliations

  1. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Stephen S. Whitehead, Joseph E. Blaney & Brian R. Murphy

  2. Department of International Health, Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA

    Anna P. Durbin

Authors
  1. Stephen S. Whitehead
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  2. Joseph E. Blaney
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  4. Brian R. Murphy
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Correspondence to Stephen S. Whitehead.

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DATABASES

Entrez Genome

DENV

JEV

TBEV

WNV

YFV

Entrez Genome Project

Aedes aegypti

Aedes albopictus

FURTHER INFORMATION

Laboratory of Infectious Diseases

Mahidol University

PAHO

Walter Reed Army Institute of Research

WHO DengueNet

Glossary

Sylvatic

A form of disease that occurs in wild animals.

Dendritic cells

A 'professional' antigen-presenting cell that is found in the T-cell areas of lymphoid tissues and as a minor cellular component in most tissues, including skin. They have a branched or dendritic morphology and are the most potent stimulators of T-cell responses.

Hypovolemia

A decrease in intravascular number.

Ascites

The accumulation of fluid in the peritoneal cavity.

Councilman bodies

An eosinophilic globule seen in the liver of individuals with viral haemorrhagic fevers, especially yellow fever. Councilman bodies result from necrosis of a single liver cell.

Adaptive immune response

Represented by B and T lymphocytes that express antigen-specific receptors. Memory lymphocytes persist, providing immunity against re-infection.

Parenteral route

A route other than the gastrointestinal route, such as intravenous, subcutaneous or intradermal.

Reverse genetic technique

A method that allows the production of viruses from cloned cDNA.

Prime–boost strategy

When a single application of a vaccine is insufficient, repeated immunizations are carried out with either the same vaccine preparation (homologous prime–boost) or different vaccine preparations (heterologous prime–boost) to sequentially stimulate a better immune response.

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Whitehead, S., Blaney, J., Durbin, A. et al. Prospects for a dengue virus vaccine. Nat Rev Microbiol 5, 518–528 (2007). https://doi.org/10.1038/nrmicro1690

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