Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation

Monica Josiane Rodrigues-Jesus; Marianna Teixeira de Pinho Favaro; Aléxia Adrianne Venceslau-Carvalho; Maria Fernanda de Castro-Amarante; Bianca da Silva Almeida; Mariângela de Oliveira Silva; Robert Andreata-Santos; Cecilia Gomes Barbosa; Samantha Carvalho Maia Brito; Lucio H Freitas-Junior; Silvia Beatriz Boscardin; Luís Carlos de Souza Ferreira

doi:10.1016/j.nano.2022.102595

Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation

Nanomedicine. 2022 Sep:45:102595. doi: 10.1016/j.nano.2022.102595. Epub 2022 Aug 27.

Authors

Affiliations

¹ Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA.
² Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Scientific Platform Pasteur/USP, University of São Paulo, São Paulo, Brazil.
³ Laboratory of Antigen Targeting for Dendritic Cells, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁴ Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Scientific Platform Pasteur/USP, University of São Paulo, São Paulo, Brazil; Laboratory of Antigen Targeting for Dendritic Cells, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁵ Retrovirology Laboratory, Immunology and Microbiology Department, Federal University of São Paulo, São Paulo, Brazil.
⁶ Phenotypic Screening Platform of the Institute of Biomedical Sciences of the University of São Paulo, São Paulo, Brazil.
⁷ Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁸ Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Scientific Platform Pasteur/USP, University of São Paulo, São Paulo, Brazil. Electronic address: [email protected].

Abstract

The development of safe and effective vaccine formulations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a hallmark in the history of vaccines. Here we report a COVID-19 subunit vaccine based on a SARS-CoV-2 Spike protein receptor binding domain (RBD) incorporated into nano-multilamellar vesicles (NMV) associated with monophosphoryl lipid A (MPLA). The results based on immunization of C57BL/6 mice demonstrated that recombinant antigen incorporation into NMVs improved antibody and T-cell responses without inducing toxic effects under both in vitro and in vivo conditions. Administration of RBD-NMV-MPLA formulations modulated antigen avidity and IgG subclass responses, whereas MPLA incorporation improved the activation of CD4⁺/CD8⁺ T-cell responses. In addition, immunization with the complete vaccine formulation reduced the number of doses required to achieve enhanced serum virus-neutralizing antibody titers. Overall, this study highlights NMV/MPLA technology, displaying the performance improvement of subunit vaccines against SARS-CoV-2, as well as other infectious diseases.

Keywords: Lipid-based nanoparticles; Nano-multilamellar vesicles; RBD; SARS-CoV-2; Vaccine.

Publication types

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

MeSH terms

Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Immunity
Immunoglobulin G
Lipids
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
SARS-CoV-2*
Spike Glycoprotein, Coronavirus
Vaccines, Subunit

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Lipids
Spike Glycoprotein, Coronavirus
Vaccines, Subunit
spike protein, SARS-CoV-2