世界首支登革热疫苗开始三阶临床试验

The first dengue vaccine¹ candidate (CYD-TDV) to reach phase 3 clinical testing has shown moderate protection (56%) against the disease in Asian children, according to new research published in The Lancet. Dengue is a mosquito-borne disease that infects around 390 million people each year, of whom about 96 million suffer from symptomatic infection. WHO estimates that the global burden of dengue has risen 30-fold over the past 50 years, with over half of the world's population at risk of the disease.

 

There is no licensed² vaccine available to treat or prevent dengue fever, and efforts to develop one have been complicated by the fact that dengue is caused by four distinct dengue viruses, and a vaccine must target all four serotypes (DENV 1-4).

 

This phase 3 trial took place in dengue-endemic areas across five countries in Asia, a region that accounts for over 70% of the global dengue burden. The study involved 10 275 healthy children aged³ 2 to 14 years who were randomly⁴ assigned to receive three injections of the CYD-TDV vaccine (6851) or a placebo⁵ (3424) at 0, 6, and 12 months, and followed for up to 2 years.

 

The researchers recorded 250 dengue cases more than 28 days after the third injection -- 117 in the vaccine group and 133 in the placebo group, demonstrating an overall protective efficacy of 56.5%.

 

The vaccine also showed 88.5% efficacy（功效） after 3 doses against severe disease (dengue haemorrhagic fever) which leads to hospitalisation for over half a million people (mostly children) every year, and 67% against dengue-associated hospitalisation.

 

The researchers found that the vaccine gave low protection (35%) against DENV 2, but more than 75% protection against DENV 3 and 4, and 50% against DENV 1.

 

The vaccine was generally well tolerated. A total of 647 serious adverse⁶ events were reported, 402 (62%) in the vaccine group and 245 (38%) in the placebo group.

 

According to lead author Dr Maria Rosario Capeding from the Research Institute for Tropical Medicine in the Philippines, "Our results suggest that vaccination⁷ with CYD-TDV can reduce the incidence of symptomatic dengue infection by more than half and importantly reduced severe disease and hospitalisations. This candidate vaccine has the potential to have a significant impact on public health in view of the high disease burden in endemic countries."

 

Writing in a linked Comment, Professor Annelies Wilder-Smith from Lee Kong Chian School of Medicine, Nanyang Technological⁸ University, Singapore says, "Perhaps the most interesting finding of this trial was that efficacy after at least one dose was almost as high as that after three doses…Because three doses 6 months apart is an inconvenient⁹ and costly¹⁰ immunisation schedule for scale up in national programmes, the question of whether sufficient efficacy can be achieved with a lower number of doses deserves further assessment¹¹."

 

She adds, "With an estimated 96 million clinically apparent dengue infections annually¹², a reduction by half would present a significant public health benefit that would support dengue vaccine introduction….Whether the armamentarium of alternative vaccine candidates presently in the pipeline¹³ (including inactivated¹⁴, live attenuated¹⁵, chimeric¹⁶, recombinant, subunit and DNA¹⁷ vaccines) will improve efficacy beyond 56% remains¹⁸ to be established. For the moment, the CYD-TDV vaccine is the best we have; however, with 56% efficacy it will never be a single solution. Continued support for the development of other novel strategies including drugs, improved case management, insecticides, and new approaches to vector（矢量，带菌者） control, is needed before effective dengue control becomes a credible¹⁹ prospect²⁰.

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