Cristina Elisa Martina is now a Research Associate Professor at theVanderbilt University, Nashville, USA. She is a former member of the MBPEL laboratory.

Abstract

Alphaviruses cause either encephalitic or arthritogenic disease, depending on the strain. Encephalitic disease is associated with New World strains, including Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), and Venezuelan equine encephalitis virus (VEEV). Arthritogenic disease is caused by Old World strains, such as Chikungunya virus (CHIKV), Mayaro virus (MAYV), and Ross River virus (RRV). Currently, the only FDA-approved alphavirus vaccine targets CHIKV and does not provide cross-protection against other strains.

In this study, we leverage AI-driven computational design to develop immunogen candidates capable of eliciting broad-spectrum protection against both encephalitic and arthritogenic alphaviruses. Using epitope-focused techniques such as glycan masking and scaffolding, we enhance immune responses against conserved epitopes targeted by broadly neutralizing antibodies (e.g., SKT-05, RRV-12, CHK-265). Additionally, we employ natural and artificially designed adaptor proteins to display multiple immunogen candidates simultaneously and load them onto a nanoparticle platform to optimize immunogenicity.

Through iterative in silico and in vitro validation, we have identified promising candidates now ready for in vivo testing to evaluate their potential as a broad-spectrum alphavirus vaccine.