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

Aléxia Adrianne Venceslau-Carvalho; Marianna Teixeira de Pinho Favaro; Lennon Ramos Pereira; Mônica Josiane Rodrigues-Jesus; Samuel Santos Pereira; Robert Andreata-Santos; Rúbens Prince Dos Santos Alves; Maria Fernanda Castro-Amarante; Karine Bitencourt Rodrigues; Jamile Ramos da Silva; Rafael Rahal Guaragna Machado; Marielton Dos Passos Cunha; Paolo Marinho de Andrade Zanotto; Wesley Luzetti Fotoran; Gerhard Wunderlich; Edison Luiz Durigon; Luís Carlos de Souza Ferreira

doi:10.1016/j.nano.2021.102445

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

Nanomedicine. 2021 Oct:37:102445. doi: 10.1016/j.nano.2021.102445. Epub 2021 Jul 22.

Authors

Aléxia Adrianne Venceslau-Carvalho¹, Marianna Teixeira de Pinho Favaro², Lennon Ramos Pereira³, Mônica Josiane Rodrigues-Jesus⁴, Samuel Santos Pereira⁵, Robert Andreata-Santos⁶, Rúbens Prince Dos Santos Alves⁷, Maria Fernanda Castro-Amarante⁸, Karine Bitencourt Rodrigues⁹, Jamile Ramos da Silva¹⁰, Rafael Rahal Guaragna Machado¹¹, Marielton Dos Passos Cunha¹², Paolo Marinho de Andrade Zanotto¹³, Wesley Luzetti Fotoran¹⁴, Gerhard Wunderlich¹⁵, Edison Luiz Durigon¹⁶, Luís Carlos de Souza Ferreira¹⁷

Affiliations

¹ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: alexiabiotec@usp.br.
² Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: favaro.mtp@gmail.com.
³ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: lennon_rp@hotmail.com.
⁴ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: modrigues4@gmail.com.
⁵ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: samuelbiomedicina@usp.br.
⁶ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: robert_andreata@hotmail.com.
⁷ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: rubens.bmc@gmail.com.
⁸ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: mfamarante@gmail.com.
⁹ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: karinebitencourt@usp.br.
¹⁰ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: jamile@usp.br.
¹¹ Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: rafaelmachado@usp.br.
¹² Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil. Electronic address: marieltondospassos@gmail.com.
¹³ Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil. Electronic address: pzanotto@usp.br.
¹⁴ Unit for Drug Development and Plasmodium Molecular Biology, Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, Brazil. Electronic address: wesleylfw@hotmail.com.
¹⁵ Unit for Drug Development and Plasmodium Molecular Biology, Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, Brazil. Electronic address: gwunder@usp.br.
¹⁶ Laboratory of Clinical and Molecular Virology, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: eldurigo@usp.br.
¹⁷ Vaccine Development Laboratory, Microbiology Department and Parasitology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: lcsf@usp.br.

PMID: 34303841
DOI: 10.1016/j.nano.2021.102445

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 ∆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.

Keywords: CHIKV; Chikungunya; MPLA; NMVs; Nanovaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / biosynthesis
Antibodies, Neutralizing / drug effects
Antibodies, Neutralizing / immunology
Antibodies, Viral / biosynthesis
Antibodies, Viral / drug effects
Antibodies, Viral / immunology
Chikungunya Fever / immunology*
Chikungunya Fever / therapy
Chikungunya Fever / virology
Chikungunya virus / immunology*
Chikungunya virus / pathogenicity
Humans
Liposomes / chemistry
Liposomes / immunology*
Liposomes / pharmacology
Mice
Nanoparticles / chemistry
Viral Envelope Proteins / genetics*
Viral Envelope Proteins / pharmacology
Viral Vaccines / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Lipid Nanoparticles
Liposomes
Viral Envelope Proteins
Viral Vaccines