Dengue fever ranks behind malaria in the pantheon of deadly mosquito-borne tropical illnesses. But both afflictions have one important thing in common: there's no commercially available vaccine to protect those at risk.
Because dengue is caused by one of four kinds of closely related viruses, it's been especially difficult to develop a single vaccine versatile enough to protect against it. Now, an international team of researchers says they've made a breakthrough, but the vaccine has turned out much less potent than observers had hoped.
In a trial of 4002 Thai schoolchildren, the overall efficacy of a dengue vaccine developed by Sanofi Pasteur was a disappointing 30%, according to a paper published in The Lancet on Monday.
The efficacy rate of the vaccine is calculated based on the difference between the percentage of children in the vaccine group that developed dengue versus the control group - 2.8% and 4.4%, respectively. In this case, the results for overall efficacy against all four types of virus weren't statistically significant.
However, secondary testing showed the vaccine worked against three of the four viruses that cause the disease. For DENV1, DENV3, and DENV4, the researchers calculated vaccine efficacy rates of 56%, 75%, and 100%, respectively, but found a mere 9% efficacy rate for DENV2.
"Although the assumed high efficacy against all four serotypes of dengue virus was not shown, our study constitutes the first ever demonstration that a safe dengue vaccine is possible," the authors wrote.
"This trial is a cautionary tale for investigators designing future dengue vaccine efficacy trials," Scott Halstead, an adviser for the Dengue Vaccine Initiative at the International Vaccine Institute in South Korea, wrote in an accompanying commentary.
The researchers speculated in their paper that the genetic code of DENV2 that was used in the vaccine may have differed from the genotype of the DENV2 strain that was circulating at the time, resulting in ineffective antibodies against that virus.
"Dengue vaccine development, although increasingly based on new abilities to understand and manipulate viral genomes, remains an empirical process from the standpoint of efficacy and safety," Halstead wrote. "Serious deficits remain in our understanding of the mechanism or mechanisms by which human beings are protected against initial and successive infections with the four DENV."
Still, Halstead said, a vaccine against 3 out of 4 dengue viruses could possibly be used to wage a strategic campaign against the disease. Severe dengue outbreaks are known to require the presence of multiple kinds of viruses in circulation, so knocking out three-quarters of the players could spell doom for the remaining one.
SOURCE: Sabchareon et al. "Protective efficacy of therecombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomized, controlled phase 2b trial"; Halstead, Scott. "Dengue vaccine development: a 75% solution?" The Lancet published online 11 September 2012.