groups » Dengue Vaccine Discussion Group » Expert comment wanted on: 'Dengue vaccine worsens disease'
We have seen some concerning headlines this week about the dengue vaccine (see below) and would like to interview an expert who could explain this to the general public.
Through an article on Break Dengue, perhaps it would be possible to explain why a second infection is worse than the first infection. And then to say what this means for vaccination programs?
This story seems to be getting quite serious. I would welcome any informed comment which might help our audience make sense of it
Dengue is a complex of four serotypes, designated DENV1, 2, 3, 4. An individual infected with one serotype, say DENV 2, develops long-lasting protective immunity against serotype 2. Protection against the other serotypes, however (in this case 1, 3 and 4), is usually short-lived and weak. This is because, in many cases, antibodies against the other virus serotypes due to this infection are not at levels where they can neutralize them (prevent them from infecting cells).
These non-neutralizing antibodies, therefore, are what are thought to put the infected individual at risk of severe disease if he or she gets infected with the other serotypes, through a process called antibody-dependent enhancement (ADE). This effect has been demonstrated with lab animals, which, when challenged a second time with a different serotype developed severe disease; the virus multiplied faster and reached higher titers in the second instance.Severe dengue has also been significantly higher in infants whose maternally acquired antibody levels had diminished to levels that were no longer protective. It is thought that the weakly binding antibodies act as a "Trojan horse" for the virus, which is then more efficiently taken up by the cells with antibody receptors, the main targets for the virus.
In individuals with prior dengue infection, the vaccine may boost pre-existing immunity, and so protect against severe disease or hospitalization. In naive people, however, such as young children with no prior exposure, infection or pre-existing immunity, the vaccine may not elicit adequate antibody responses against all four serotypes equally. ADE, and subsequent severe disease, therefore, is a potential risk.