Why So Difficult To Develop Vaccine For Dengue Virus ?

• It's not as simple as with measles and mumps: dengue is actually caused by 4 related but entirely individual viruses (dengue 1 - 4), which differ in their antigenicity, meaning that any vaccine you develop must protect against not 1 virus, but 4. All measles and mumps viruses are considered antigenically the same; one virus = one vaccine.   

• We don't actually know what makes a good dengue vaccine: is it high antibody levels? Cytotoxic T cells? Where must you evoke immunity? How do you know you're successful if you don't know what successful is? 

• Antibody-dependent enhancement of infection is a serious problem with dengue: the most severe form of the disease is caused by your re-infection with another type of dengue than the one you orginally were infected with. It appears that those antibodies you made in the first place cause the virus to replicate more. This means that if the vaccine protected against some of the types more efficiently than others, you could cause serious adverse reactions following natural dengue infection. We need a balanced immunity. And, whats going to happen as your antibody levels decrease as you get older, will that leave you open to the more severe dengue in later life? Will we have to vaccinate continuously? Will antibody-dependent enhancement of infection cause those vaccine viruses to cause more disease? Another case for the need to develop four, long-lived vaccines in one. 

• There is no animal model out there which fully replicates what we see in humans. This further hampers any work we do on how the virus replicates in us and how we can prevent this with vaccinating. 

• Then there's the logistic problems of first producing a vaccine at sufficiently large scales and then going out and distributing it to some of world's most inaccessible populations, in some of world's most harshest conditions (to vaccines anyway). At least maybe we can learn from the lessons from other vaccines in this respect. 

• Clinical trials are not cheap. Period. Nor is any testing and production of any vaccine.

• We don't want any reversion to virulent virus. The use of live-attenuated viruses, especially RNA ones, always holds the risk of a genetic mutation turning your nice and safe vaccine virus back into its deadly counterpart.