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.
Zika Transmission and Early Understanding
Zika virus spreads primarily through the bite of infected Aedes mosquitoes, which mostly bite during the day. It can also spread through sex and from an infected mother to a fetus during pregnancy. The CDC reports that infection during pregnancy can cause certain birth defects, while the WHO notes that most infected people do not develop symptoms and that symptoms, when present, typically last 2–7 days.
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.
Dengue History Shapes Zika B-Cell Responses
Research in rhesus macaques examined how prior dengue virus serotype 3 infection affects later plasmablast responses to Zika virus infection. The study reports that Zika-reactive plasmablasts from dengue-immune donors had more biased clonal repertoires and greater specificity for previous viruses than plasmablasts from individuals with primary Zika infections. These findings suggest that flavivirus infection history can influence subsequent B-cell immunity.
Limits of Cross-Reactive Protection
A study of dengue-experienced donors found that Zika virus activates both new and cross-reactive memory B-cell responses. The cross-reactive responses were poorly neutralizing in the reported experiments. They were also associated with enhanced Zika infection in vitro, leading the authors to suggest that preexisting dengue immunity could negatively affect protective antibody responses to Zika.
Antibody Binding After Dengue Exposure
In ELISA binding studies, between 50% and 75% of monoclonal antibodies isolated from dengue-experienced donors bound to whole Zika virus. The reported percentage was similar to the proportion of antigen-specific monoclonal antibodies recovered from plasmablasts induced by influenza vaccination and dengue infection. Binding to whole Zika virus demonstrates recognition, but the source does not establish that these antibodies were protective or strongly neutralizing.
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.