Zika vs. Dengue: Why Prior Exposure Matters for Immunity
"Decoding how past dengue infections shape the body's defense against Zika."
Zika virus (ZIKV), a mosquito-borne flavivirus, has been linked to microcephaly and severe neurological complications. Like other flaviviruses, including dengue virus (DENV), it results in substantial immunological cross-reactivity, which also means that immunity to one can affect your response to another.
Areas where dengue is common are also seeing Zika, and a key question arises: How does prior DENV exposure shape the B cell response to ZIKV? Understanding this could be a game-changer for creating vaccines and therapies that work.
Previous studies highlight the importance of three proteins in flavivirus immune responses: NS1, E, and prM. The envelope (E) protein is the main target for neutralizing antibodies. In a new study published in Science Immunology, researchers tracked how the immune system responds to Zika in people who had previously been exposed to dengue.
Dengue's Imprint: Shaping the Early Zika Response
To see how past dengue infections affect the early response to Zika, scientists followed three individuals from a dengue-prone area in Colombia who contracted Zika. For comparison, they included a Zika-infected person from the United States who had never had dengue. The main goal? To dissect the B cell response – the part of the immune system that creates antibodies to fight infections.
- Relatively high levels of somatic hypermutation (SHM), indicating a memory B cell response.
- A bias toward DENV binding and neutralization.
- Evidence for original antigenic sin (OAS). This suggests that the immune system initially recalls and amplifies existing DENV-specific B cells.
The Long Game: Memory B Cells and Antibody Evolution
Five months post-infection, the plot thickened. The dengue-experienced individuals developed type-specific ZIKV neutralizing antibody responses alongside DENV cross-reactive responses. These cross-reactive antibodies, however, were poorly neutralizing and sometimes enhanced ZIKV infection in lab tests.
This raises a critical concern: pre-existing DENV immunity might negatively affect protective antibody responses to ZIKV, depending on the specific epitopes targeted. It seems that the immune system's initial focus on dengue-related responses might compromise its ability to mount an effective de novo ZIKV response, at least in some individuals.
These findings underscore the need for careful ZIKV vaccine design, especially for those living in dengue-endemic regions. Vaccines should aim for ZIKV-specific epitopes to avoid skewing the immune response towards less effective, cross-reactive antibodies. It's a delicate balancing act, but understanding these immune dynamics is vital for creating effective and safe ZIKV vaccines.