Cross-Reactive Immunity among Five Medically Important Mosquito-Borne Flaviviruses Related to Human Diseases

Flaviviruses cause a spectrum of potentially severe diseases. Most flaviviruses are transmitted by mosquitoes or ticks and are widely distributed all over the world. Among them, several mosquito-borne flaviviruses are co-epidemic, and the similarity of their antigenicity creates abundant cross-reactive immune responses which complicate their prevention and control. At present, only effective vaccines against yellow fever and Japanese encephalitis have been used clinically, while the optimal vaccines against other flavivirus diseases are still under development. The antibody-dependent enhancement generated by cross-reactive immune responses against different serotypes of dengue virus makes the development of the dengue fever vaccine a bottleneck. It has been proposed that the cross-reactive immunity elicited by prior infection of mosquito-borne flavivirus could also affect the outcome of the subsequent infection of heterologous flavivirus. In this review, we focused on five medically important flaviviruses, and rearranged and recapitulated their cross-reactive immunity in detail from the perspectives of serological experiments in vitro, animal experiments in vivo, and human cohort studies. We look forward to providing references and new insights for the research of flavivirus vaccines and specific prevention.

Automated summary

Flaviviruses, transmitted by mosquitoes or ticks, cause a range of severe diseases globally. The similarity of antigenicity among several mosquito-borne flaviviruses complicates prevention and control due to cross-reactive immune responses. Effective vaccines are only available for yellow fever and Japanese encephalitis, while vaccines for other flavivirus diseases are still in development. The development of a dengue fever vaccine is hindered by antibody-dependent enhancement caused by cross-reactive immune responses. Cross-reactive immunity from prior infection of mosquito-borne flavivirus may also impact the outcome of subsequent heterologous flavivirus infection.