Progress towards a dengue vaccine

8 Dec 2009

Paul Chinnock

Source: Lancet Infectious Diseases (see original article or PDF)

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Citation: Webster DP, Farrar J, Rowland-Jones S (2009). Progress towards a dengue vaccine. Lancet Infect Dis; 9(11):678-687.

2009 Elsevier Limited

This severity of this year’s dengue fever epidemics has raised to a new level the widespread public concern over the continuing rise of this disease. According to newspaper reports from some large cities in Asia and Latin America, the sheer number of recent cases is causing panic in many communities. Increasingly, people in such communities are asking how it can be that the world has failed to develop either a specific treatment or a vaccine for dengue.

It is an appropriate time then for the publication of a review article that attempts to sum up what is known about dengue pathogenesis and the implications for vaccine design, current progress in vaccine development, and the challenges that lie ahead. The article, by Daniel Webster, Jeremy Farrar and Sarah Rowland-Jones, appears in Lancet Infectious Diseases.

The authors attribute the rise of dengue largely to increased urbanisation and the failure to control the main disease vector – the Aedes aegypti mosquito. They point out that, while traditionally most dengue patients have been children, adults are increasingly falling victim. Control of dengue through vaccination was identified as a priority by WHO three decades ago and – given that vaccines are available for related flaviviruses such as yellow fever, Japanese encephalitis virus and tick-borne encephalitis virus – the lack of progress has been disappointing. As there are four serotypes of the dengue virus, what is needed is a vaccine that confers high levels of protection against all of them.

It is believed that after a dengue infection, robust neutralising antibody responses develop that provide lifelong protection against reinfection with the same dengue serotype. (Protection against other serotypes is only temporary.) The existence of this naturally acquired immunity suggests that an effective dengue vaccine should be feasible. Dengue-specific cellular immunity is, however, less well defined. The authors go on to describe recent research in the immunopathology of dengue, which have led to important advances in understanding.

The greater part of the article is given over to a description of eleven potential vaccines now under development. The authors consider the leading candidate to be Sanofi Pasteur’s chimeric vaccine, ChimeriVax; three independent, phase 1 clinical trials have been done in Australia and USA in animals unexposed or immune to flaviviruses. Other candidate vaccines belong to a range of vaccine types: live attenuated, infectious clone, inactivated, replication incompetent, protein, DNA and virus vector. Several of these vaccines have shown promise in phase 2 clinical trials. The authors also provide a list of the characteristics that the ideal dengue vaccine would possess.

In the opinion of the authors there has been a lack of coordination in vaccine development efforts to date. Nevertheless, they conclude that:

“The opportunity now exists to bring effective and safe dengue vaccines to populations at greatest risk, and there is unprecedented momentum to bring about a coordinated worldwide effort.”

In the same issue of Lancet Infectious Diseases a news article describes the launch of the first full-scale efficacy trial to test the ChimeriVax vaccine. This will take place in Ratchaburi, Thailand, with the enrolment of about 4000 4–11-year-old children. The first findings are expected in 2012,

Sadly, neither article is available with open access. To read them in full a subscription to the journal is required. (In some developing countries, access may be possible through HINARI.)