ROUND-UP: Results of dengue vaccine trial (The Lancet) – experts respond

Tue Sep 11, 2012

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EMBARGO LIFTED 9am AEST Tue 11 September, 2012

Researchers from France and Thailand have trialled a dengue vaccine in over 4000 Thai children. While overall there was no difference between the number of dengue cases recorded following vaccination, secondary tests showed that the vaccine was effective against three of the four dengue viruses, providing hope that an effective and safe dengue vaccine may be possible. Dengue is not caused by a single virus, but rather by four different related viruses (known as DENV 1, 2, 3 and 4), making development of an effective vaccine considerably more complicated than for some viral diseases. Dengue is one of the most widespread mosquito-borne viral diseases in the world, with WHO estimating that around half of the world’s population are currently at risk. In Australia, dengue currently occurs in north Queensland although cases have been reported historically in the Northern Territory and New South Wales. There is currently no vaccine to protect against dengue.

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Professor Scott O’Neill is Dean of Science and Chief Investigator on the Eliminate Dengue Program at Monash University.

 

“The question is, is the glass half-empty or half-full? True the vaccine shows protection against three of the strains, but unfortunately—and this is very disappointing — overall it was not effective, showing no protection for the most common dengue strains circulating in Thailand. This is a very disappointing result for people interested in dengue that have been following this research – we were all hoping for a much stronger result. The current data suggest that there is still more work needed on dengue vaccine development. 

 

Our team is working on an alternative approach which could be used in unison with a vaccine to help make it more effective. We’ve developed a way to stop mosquitoes from transmitting the virus. We infect the mosquitoes with a naturally occurring bacterium called Wolbachia and this reduces their ability to become infected with dengue. We’re currently testing our technique in real-life situations in Queensland, Vietnam, Indonesia and Brazil.”

* Note – Scott is on a plane to Colombia today and will be out of contact

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Professor Cameron Simmons is a Wellcome Trust Senior Research Fellow at the Centre for Tropical Medicine, Oxford University Clinical Research Unit in Vietnam

“Dengue is a mosquito-carried viral disease that afflicts ~100 million people, mainly children, every year. Dengue is a constant disease threat to Australian travellers visiting SE Asia and Latin America, and in turn, to residents of Far North Queensland when returned travellers with dengue generate local epidemics in their communities. Those unlucky enough to have had dengue will attest to the moniker ‘break-bone fever’ being an accurate description of this miserable illness. Thus, the announcement of results from the first large-scale field trial of a dengue vaccine in ~4000 Thai children by the drug company Sanofi Pasteur is a wonderful step forward in the fight against this public health menace.

 

The study results indicated the vaccine was safe but somewhat disappointingly provided protection against only 3 of the 4 dengue viruses that infect humans. Further large-scale testing of this vaccine is ongoing with the hope of creating pivotal evidence of protection against all four of the dengue viruses. For dengue, the ‘holy grail’ has always been to create a cheap, safe, simple to use and effective vaccine. The results obtained in this current trial suggest the holy grail, while still elusive, is one small step closer.”

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Professor Suresh Mahalingam is an ARC Future Fellow and Principal Research Leader of the Emerging Viruses and Inflammation Research Group at Griffith University

 “Antibody-dependent enhancement (ADE) is the phenomenon in which non-neutralising antiviral antibodies cause enhanced viral infection of host cells. There are a number of epidemiological studies that show that dengue haemorrhagic fever occurs in patients who have undergone a secondary dengue infection. This is one of the major challenges in the development of an effective dengue vaccine. However, ADE has largely been described in vitro and it has been difficult to demonstrate its clinical relevance to dengue infection. Nevertheless ADE poses difficulties for efforts to develop dengue vaccines. A suitable vaccine against dengue should provide long term immunity with antibody responses effective against all the four DV serotypes, without development of sub-neutralizing antibodies that may induce ADE.

 This recent study is a major breakthrough as their candidate vaccine was immunogenic for all four serotypes and protected against three of the four serotypes (1, 3, and 4). Importantly, there was no sign of enhanced disease with this vaccine showing great promise.”

 
[* Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial, Sabchareon, et al., The Lancet, Published online September 11, 2012]