Neutralizing monoclonal antibodies against dengue virus: a scoping review of preclinical and clinical development

Background

Dengue virus (DENV) is a major global health challenge, causing over 7.6 million reported cases in 2024. Neutralizing monoclonal antibodies (NmAbs) have emerged as promising therapeutics to address the limitations of vaccines and lack of antivirals, but their development is complicated by viral diversity, “breathing” dynamics, and antibody-dependent enhancement (ADE).

Objectives

This scoping review aimed to map and synthesize evidence on NmAbs targeting DENV, summarizing their epitopes, mechanisms, serotype coverage, neutralization potency, and development status.

Methods

We searched PubMed (to June 2025) for studies characterizing NmAbs with in vitro or in vivo DENV neutralization. Inclusion required primary data on neutralizing activity. Data extraction included antibody origin, epitope, potency, ADE risk, and clinical progress.

Results

Fifty-six studies were included, covering more than 30 NmAbs. Fusion loop–directed antibodies (e.g., 3G9, E53) display broad reactivity but frequently mediate ADE unless Fc-modified. E-dimer epitope (EDE) antibodies (A11, B7, C8, C10) recognize quaternary epitopes with high in vitro potency, though evidence for in vivo protection and ADE avoidance remains limited. Domain III–directed antibodies (e.g., m366.6, 1C19) show serotype-spanning activity, while others such as 2D22 or DENV-290 exhibit potent type-specific neutralization. Several candidates demonstrate efficacy in animal models, and two human antibodies, VIS513 and AV-1, have advanced to clinical evaluation, with VIS513 completing Phase 1 trials.

Conclusions

NmAbs offer a promising adjunct to dengue care but require careful epitope selection and Fc engineering to balance potency and safety. Continued preclinical and clinical evaluation is essential to advance these candidates toward therapeutic use.