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Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines. A vaccine composed of nano-multilamellar lipid vesicles (NMVs) carrying a new recombinant protein based on the Chikungunya virus (CHIKV) E2 protein, ∆E2.1, increases antibody titers in mice and is capable of generating antibodies that neutralize CHIKV in vitro, demonstrating the effectiveness of both the new antigen generated and the NMVs delivery system. [Display omitted] • A novel CHIKV antigen derived from the envelope protein (∆E2.1) was successfully expressed and easily purified from recombinant Escherichia coli cells. • The ∆E2.1 antigen maintained the antigenicity of the native virus protein and was efficiently recognized by antibodies present in CHIKV-infected convalescent patients. • The ∆E2.1 antigen was formulated in adjuvanted nano-multilamellar vesicles (NMV-MPLA) that promoted a depot effect with a controlled release of the antigen. • The ∆E2.1-NMV-MPLA vaccine formulation was highly immunogenic in mice and induced serum antibodies that were capable of neutralizing CHIKV under in vitro conditions. [ABSTRACT FROM AUTHOR]