Adjuvant-free biopolymer particles mimicking the Chikungunya virus surface induce protective immunity.

Abstract

Chikungunya virus, a mosquito-borne alphavirus, causes outbreaks of both acute and chronic musculoskeletal diseases. Despite the recent approval of a live-attenuated and virus-like particle-based vaccine, a stable, safe and efficacious vaccine that can be manufactured at low cost is lacking. To address this need, we engineered Escherichia coli to produce robust biopolymer particles (BPs) densely coated with CHIKV envelope glycoproteins E2 and E1, forming a natively folded heterodimer mimicking the virus surface (E2-BP-E1). Native E2-E1 heterodimer formation was confirmed by monoclonal antibodies binding to five neutralizing epitopes and by binding of the receptor Mxra8. The structural model of BP-tethered E2-E1 aligned with the crystal structure of mature E2-E1 complex. In vitro, E2-BP-E1 activated dendritic cells (DCs) to produce Th1 cytokines, present MHC class I/II T cell epitopes, and stimulate CD4⁺ and CD8⁺ T cell proliferation. In vivo, vaccination without adjuvant induced potent neutralizing antibodies and protective immunity, with a ∼5 log₁₀ reduction in viremia. Histological analysis of muscle and joints confirmed reduced inflammation and pathology in vaccinated mice. E2-BP-E1 was produced using standard E. coli fermentation suggesting safe, cost-effective and scalable manufacturability offering advantages over current vaccines. Overall, we developed a stable particulate CHIKV vaccine that is safe and efficiently protects against infection without the need of an adjuvant.