Antibody responses to Japanese encephalitis virus and dengue virus serotype 2 in children from an orthoflavivirus endemic region after IMOJEV vaccination

Background Japanese encephalitis virus (JEV) is a mosquito-borne pathogen that causes severe neurologic disease. Its endemicity in Asia has prompted its inclusion in nationwide immunization programs. However, the Philippines, which is also endemic for related viruses like dengue (DENV), has not yet adopted this practice. Vaccine hesitancy is a major challenge, exacerbated by concerns over cross-reactive antibodies that may enhance viral infection. This study aimed to determine whether IMOJEV vaccination would induce cross-neutralizing or enhancing antibodies against DENV. Methodology/Principal findings Pre- and one-month post-vaccination samples from IMOJEV-vaccinated Filipino children (9–24 months old) were analyzed. A reporter virus particle (RVP)-based neutralization assay against JEV showed neutralization in 28/29 subjects post-vaccination. Presence of DENV2-reactive antibodies was measured via DENV2 VLP ELISA, which revealed increased DENV2 binding reactivity post-vaccination. Pre-vaccination DENV2 binding reactivity also had no significant correlation with the JEV vaccine response. RVP-based neutralization and enhancement assays against DENV2 showed that there was no significant change in neutralizing or enhancing antibody activity against DENV2 after JEV vaccination. Conclusions/Significance This study shows that IMOJEV vaccination elicited a JEV neutralizing response in 97% of vaccinees and that the magnitude of JEV neutralizing titers post-vaccination was not associated with pre-existing binding antibodies to DENV2. Further, while live JEV vaccination increases DENV2-binding antibodies, this cross-reactivity does not lead to DENV2 enhancement. These findings contribute to a better understanding of the orthoflavivirus antibody response following immunization and the influence of pre-existing heterologous orthoflavivirus antibodies. This could guide vaccination strategies, especially in orthoflavivirus-endemic regions.