Abstract
Both Zika virus (ZIKV) and four serotypes of dengue virus (DENV1–4) are antigenically related mosquito-borne flaviviruses that co-circulate in overlapping geographic distributions. The considerable amino acid sequence homology and structural similarities between ZIKV and DENV1–4 may be responsible for the complicated immunological cross-reactivity observed for these viruses. Thus, a successful Zika vaccine needs to not only confer protection from ZIKV infection but must also be safe during secondary exposures with other flavivirus, especially DENVs. In this study, we used a Zika DNA vaccine candidate (pV-ZME) expressing the ZIKV premembrane and envelop proteins to immunize BALB/c mice and evaluated the potential cross-reactive immune responses to DENV1–4. We observed that three doses of the pV-ZME vaccine elicited the production of cross-reactive antibodies, cytokines and CD8+ T cell responses and generated cross-protection against DENV1–4. Our results demonstrate a novel approach for design and development of safe Zika and/or dengue vaccines.
Highlights
Both Zika virus (ZIKV) and four serotypes of dengue viruses (DENV1–4) belong to the genus Flavivirus, family Flaviviridae
The results demonstrated that the Zika DNA vaccine could elicit relatively balanced cross-reactive antibody responses to DENV1–4
Because of the complicated immunological crossreactivity among flaviviruses, it is necessary to determine the role of pre-existing ZIKV immunity in cross-reactivity to DENV infection within the same host
Summary
Both Zika virus (ZIKV) and four serotypes of dengue viruses (DENV1–4) belong to the genus Flavivirus, family Flaviviridae. These viruses are antigenically related mosquito-borne pathogens that are transmitted through the same vectors, Aedes aegypti and Aedes albopictus, and co-circulate in overlapping geographic distributions. Since 2016, with the spread of ZIKV in DENV-endemic regions in the north of Brazil, individuals infected by ZIKV were likely pre-exposed to DENV (Nogueira et al, 2018). This situation has aroused concern among researchers regarding the cross-reactive immune response resulting from pre-existing DENV immunity on Zika disease outcomes.
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