Immune cross-reactivity between Dengue and Zika viruses in two pediatric studies in Nicaragua

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.210-210.5
• Main Authors: Cruz, Magelda Montoya, Puerta-Guardo, Henry Nelson, Schildhauer, Sam, Katzeltnick, Leah, Balmaseda, Angel Lazaro, Harris, Eva
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.210.5

The 4 dengue virus (DENV) serotypes and Zika virus (ZIKV) are antigenically related mosquito-borne flaviviruses that cause human diseases of major medical and public health importance worldwide. The cross-reactivity between DENV and ZIKV has raised questions about cross-neutralization and concerns of cross-enhancement, yet few data exist characterizing the long-term antibody response. Here, we studied the extent of immunological cross-reactivity between DENV and ZIKV using samples from two long-term studies in Nicaragua: a hospital-based study with a longitudinal arm extending for 18 months and a 13-year ongoing community-based cohort study with annual healthy blood samples. We selected confirmed dengue cases, stratified by serotype (DENV1, 2, 3) and immune status (primary, secondary) (n=5/group), and analyzed plasma samples collected at acute, convalescent, 3-, 6-, 12- and 18-month time-points, as well as 1–3 years post-infection, using a Vero cell-based focus reduction neutralization assay. We found that primary DENV infections display lower levels of cross-neutralizing antibodies to ZIKV than secondary DENV infections, but that both maintain cross-reactivity over time. We noted differences by serotype, with less cross-neutralization in DENV1-immune plasma. However, when we compared these data with neutralization titers against DENV1-4, we found neutralizing antibody titers to ZIKV to be ~10-fold lower than to the homologous DENV. We are also testing Zika-positive samples with and without prior DENV exposure and samples negative for prior ZIKV or DENV infections. These findings improve our understanding of cross-neutralization over time between DENV and ZIKV, with implications for natural immunity and vaccines.