Flavivirus cross-reactivity: Insights into e-protein conservancy, pre-existing immunity, and co-infection

Abstract

Flaviviruses are enveloped, single-stranded RNA viruses that are largely arthropod-borne, circulating globally and infecting up to 400 million people annually. Their widespread distribution, shared antigenicity, and evolutionary relationships lead to immune responses that cross-react across multiple flaviviruses. This presents challenges for accurate serological diagnosis and vaccine development, especially in regions where multiple flaviviruses are endemic. Such challenges can result in direct and indirect adverse effects, including antibody-dependent enhancement (ADE) and the production of sub-neutralizing antibodies. To fully understand the mechanism of cross-reactivity among medically important flaviviruses, it is crucial to explore the underlying factors contributing to this phenomenon. These factors encompass the conservation of the envelope protein (E protein), pre-existing immunity, and co-infection of different flaviviruses. While previous reviews have often discussed these factors separately, our review aims to elucidate their interconnectedness and their combined effects on cross-reactivity across clinically significant flaviviruses.

Keywords

• Flaviviruses
• Arthropod-borne
• Cross-react
• Cross-reactivity
• Factors