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

Author(s):Show less -

Venceslau-Carvalho, Alexia Adrianne ^{[1, 2]} ; Favaro, Marianna Teixeira de Pinho ^{[1, 2]} ; Pereira, Lennon Ramos ^{[1, 2]} ; Rodrigues-Jesus, Monica Josiane ^{[1, 2]} ; Pereira, Samuel Santos ^{[1, 2]} ; Andreata-Santos, Robert ^{[1, 2]} ; Alves, Rubens Prince dos Santos ^{[1, 2]} ; Castro-Amarante, Maria Fernanda ^{[1, 2]} ; Rodrigues, Karine Bitencourt ^{[1, 2]} ; da Silva, Jamile Ramos ^{[1, 2]} ; Machado, Rafael Rahal Guaragna ^[3] ; Cunha, Marielton dos Passos ^[4] ; Zanotto, Paolo Marinho de Andrade ^[4] ; Fotoran, Wesley Luzetti ^[5] ; Wunderlich, Gerhard ^[5] ; Durigon, Edison Luiz ^[3] ; Ferreira, Lufs Carlos de Souza ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Parasitol, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Vaccine Dev Lab, Dept Microbiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Clin & Mol Virol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Mol Evolut & Bioinformat, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Unit Drug Dev & Plasmodium Mol Biol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Nanomedicine-Nanotechnology Biology and Medicine; v. 37, OCT 2021.
• Web of Science Citations: 0

Abstract

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 Delta 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 Delta 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. (C) 2021 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 17/23281-6 - The use of antibodies that neutralize infection at a post-attachment step for the development of innovative immunotherapeutic strategies exemplified for selective destruction of Zika-infected human cells.
• Grantee: Paolo Marinho de Andrade Zanotto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/19145-7 - Application of liposomes for RNA vaccines against the Plasmodium falciparum PfHR5 antigen and establishment of a technical approach for guided liposomes
• Grantee: Wesley Luzetti Fotoran
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/08204-2 - Genetic and phylodynamics diversity of emerging and re-emerging arboviruses (DENV, ZIKV and CHIKV) in the Northeast and Southeast regions of Brazil, 2014-2016
• Grantee: Marielton dos Passos Cunha
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/24769-2 - Zika virus in postpartum women and newborns: seroepidemiology and molecular characterization
• Grantee: Rafael Rahal Guaragna Machado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/20045-7 - Antigen discovery and development of serological diagnostic methods and vaccine approaches against the Zika Virus (ZIKV)
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23560-0 - Development of uniplex and multiplex diagnostic platforms for arbovirus infection using recombinant proteins
• Grantee: Robert Andreata Santos
• Support Opportunities: Scholarships in Brazil - Doctorate