# From promise to pitfalls: immunological lessons from dengue vaccines and their implications

## TL;DR

This paper reviews the challenges in developing effective dengue vaccines, focusing on immune responses and safety issues.

## Contribution

The paper provides a critical evaluation of immunological factors affecting dengue vaccine development and offers insights for future strategies.

## Key findings

- Licensed dengue vaccines show serostatus-dependent safety and protection issues.
- Serotype imbalance and cross-reactivity complicate vaccine efficacy.
- Vector-mediated immune modulation and orthoflavivirus interactions remain key obstacles.

## Abstract

Dengue continues to pose a significant global health threat. However, the development of a safe and effective tetravalent vaccine is impeded by complex serotype-specific and cross-reactive immune responses. This review assesses licensed and advanced dengue vaccines, emphasizing serostatus-dependent safety, serotype imbalance, and the durability of protection. It also critically evaluates immunological correlates of protection and addresses remaining obstacles, such as vector-mediated immune modulation and orthoflavivirus cross-reactivity, to guide future dengue vaccine strategies.