1 Sabchareon A

Wallace D

Sirivichayakul C

et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial.

2 Brady OJ

Gething PW

Bhatt S

et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus.

3 Alonso PL

Sacarlal J

Aponte JJ

et al. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.

4 Francis DP

Heyward WL

Popovic V

et al. Candidate HIV/AIDS vaccines: lessons learned from the world's first phase III efficacy trials.

5 Monath TP

Cetron MS

Teuwen DE Yellow fever vaccine.

6 Halstead SB

Thomas SJ Japanese encephalitis: new options for active immunization.

7 Murphy BR

Whitehead SS Immune response to dengue virus and prospects for a vaccine.

A completed clinical trial of vaccine efficacy should be cause for celebration for the billions of people who live in the 128 countries where dengue viruses (DENV) are transmitted.However, the celebration will be muted this time, as was the case after announcement of results of early clinical trials of vaccines for malaria and HIV.The low efficacies reported from trials of malaria and HIV vaccines were not entirely unexpected, since these pathogens are known for antigenic complexity and for their ability to successfully evade immune elimination. By contrast, each of the four DENV produces acute, self-limited infections that result in lifelong immunity. DENV are flaviviruses, members of a group of single-stranded RNA viruses that includes yellow fever and Japanese encephalitis viruses—highly effective live-attenuated vaccines have long been licensed for these two viruses that are safe and in extensive use.Over several decades, many live-attenuated dengue vaccine candidates have been derived by serial tissue culture passage, chimerisation, or the introduction of attenuating mutations.Phase 1 or 2 studies of these attenuated viruses, when tested individually, often generated excellent immunological responses leading to high optimism for vaccine efficacy.