Dengue hemorrhagic fever is a peculiar illness: rather than develop resistance, people with the fever often get sicker the second time they are infected. In a study of Thai volunteers, published in the July issue of Nature Medicine, Gavin Screaton and colleagues have discovered why.
Infection with any of the four subtypes of the dengue virus mobilizes immune cells that promote virus destruction. But in volunteers infected a second time with a different strain, immune cells seemed to be of low affinity for the infecting virus and instead mobilized mainly against previously encountered strains. This misdirected immune response barely fights off the new infection. What’s more, some immune cells seem to self-destruct, exacerbating the problem.
The phenomenon, dubbed ‘original antigenic sin’, presents a barrier to vaccine development. Any vaccine could in principle act like an original infection, and could promote dengue infection instead of protecting against it. The new results should help break down barriers to vaccine development for this mosquito-borne disease.
Worldwide, hundreds of thousands of people contract dengue hemorrhagic fever each year, and many require hospitalization. Most of the deaths from this virus occur after a second infection.
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(C) Nature Medicine press release.
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