# Venezuelan Equine Encephalitis Virus: Structural Biology, Vaccines, and Advances in Functional Antibodies

## TL;DR

This paper reviews the structural biology, vaccines, and functional antibodies for Venezuelan equine encephalitis virus to guide future prevention and treatment strategies.

## Contribution

The paper integrates structural insights with advances in antibody and vaccine engineering for VEEV.

## Key findings

- VEEV's structural proteome includes E1/E2 glycoproteins and Capsid, with a focus on LDLRAD3 receptor interaction.
- Vaccine strategies include live-attenuated, VLP, and nucleic acid platforms aimed at inducing neutralizing antibodies.
- Effective therapeutic antibodies require both neutralization and Fc effector functions, especially targeting fusion loops or receptor-binding sites.

## Abstract

Background: Venezuelan equine encephalitis virus (VEEV) poses a significant public health and biodefense threat due to periodic epidemics of severe neurological disease in the Americas, yet no licensed human vaccines or specific antiviral therapies exist. Methods: We comprehensively reviewed the current literature across three core domains: structural biology, vaccine development, and therapeutic antibodies. Results: First, we detail the complex viral structural proteome (including E1/E2 glycoproteins and Capsid), focusing on the LDLRAD3 entry receptor interaction. Second, we overview vaccine strategies, covering live-attenuated, VLP, and nucleic acid platforms designed to induce robust neutralizing antibodies. Finally, we examine the evolution of therapeutic antibodies, highlighting that optimal protection often relies on both neutralization and Fc effector functions, particularly for antibodies targeting the fusion loop or receptor-binding sites. Conclusions: Integrating structural insights with advanced antibody and vaccine engineering is essential for establishing effective clinical interventions capable of preventing future outbreaks and treating infected individuals.