Cross-Reactive Neutralizing Antibodies Between ZIKV and DENV May Exhibit Serotype Specificity

Dengue virus (DENV) and Zika virus (ZIKV) are public health threats, causing substantial morbidity and mortality worldwide. The co-circulation of DENV and ZIKV complicates prevention and control efforts, highlighting the importance of studying cross-reactive antibodies, vaccines, and immune modulators. This study explores the cross-reactivity and neutralizing capacity of antibodies against DENV elicited by immunization with a ZIKV protein extract. Female isogenic BALB/c mice were immunized with ZIKV protein extract derived from C6/36 cell cultures. Splenic B lymphocytes from immunized mice were fused with myeloma cells using polyethylene glycol (PEG) to generate hybridomas. The resulting antibodies were assessed using ELISA and plaque reduction neutralization tests (PRNT) against ZIKV and DENV including their structural and nonstructural proteins. Our findings showed that immunization induced a diverse antibody response, including antibodies recognizing epitopes unique to ZIKV as well as epitopes shared with DENV. Notably, neutralizing antibodies targeting conserved epitopes, particularly those shared with DENV-1, were also identified against other DENV serotypes. These results suggest the presence of cross-reactive neutralizing antibody responses between ZIKV and DENV, potentially exhibiting serotype-specific reactivity. Collectively, this study provides experimental evidence of flavivirus cross-reactivity and contributes to a more refined understanding of humoral responses in settings where these viruses co-circulate.