Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies

• Published in: Nanomedicine Vol. 37; p. 102445
• Main Authors: Venceslau-Carvalho, Aléxia Adrianne, Teixeira de Pinho Favaro, Marianna, Ramos Pereira, Lennon, Rodrigues-Jesus, Mônica Josiane, Santos Pereira, Samuel, Andreata-Santos, Robert, dos Santos Alves, Rúbens Prince, Castro-Amarante, Maria Fernanda, Bitencourt Rodrigues, Karine, Ramos da Silva, Jamile, Rahal Guaragna Machado, Rafael, dos Passos Cunha, Marielton, Marinho de Andrade Zanotto, Paolo, Luzetti Fotoran, Wesley, Wunderlich, Gerhard, Durigon, Edison Luiz, de Souza Ferreira, Luís Carlos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021
• Subjects: Animals; Antibodies, Neutralizing - biosynthesis; Antibodies, Neutralizing - drug effects; Antibodies, Neutralizing - immunology; Antibodies, Viral - biosynthesis; Antibodies, Viral - drug effects; Antibodies, Viral - immunology; Chikungunya; Chikungunya Fever - immunology; Chikungunya Fever - therapy; Chikungunya Fever - virology; Chikungunya virus - immunology; Chikungunya virus - pathogenicity; CHIKV; Humans; Liposomes - chemistry; Liposomes - immunology; Liposomes - pharmacology; Mice; MPLA; Nanoparticles - chemistry; Nanovaccine; NMVs; Viral Envelope Proteins - genetics; Viral Envelope Proteins - pharmacology; Viral Vaccines - immunology; Chikungunya; NMVs; Nanovaccine; MPLA; CHIKV
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2021.102445

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.