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2030-12-31
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NANOPARTICLE-BASED DNA VACCINE PROTECTS AGAINST SARS-COV-2 VARIANTS IN FEMALE PRECLINICAL MODELS
Guimarães, Lays Cordeiro et al. | Data do documento: 2024
Autor(es)
Guimarães, Lays Cordeiro
Costa, Pedro Augusto Carvalho
Scalzo Júnior, Sérgio Ricardo Aluotto
Ferreira, Heloísa Athaydes Seabra
Braga, Ana Carolina Soares
Oliveira, Leonardo Camilo de
Figueiredo, Maria Marta
Shepherd, Sarah
Hamilton, Alex
Queiroz-Junior, Celso Martins
Silva, Walison Nunes da
Silva, Natália Jordana Alves da
Alves, Marco Túllio Rodrigues
Santos, Anderson Kenedy
Faria, Kevin Kelton Santos de
Marim, Fernanda Martins
Fukumasu, Heidge
Birbrair, Alexander
Carvalho, Andréa Teixeira de
Aguiar, Renato Santana de
Mitchell, Michael J.
Teixeira, Mauro Martins
Costa, Vivian Vasconcelos
Frezard, Frederic
Guimaraes, Pedro Pires Goulart
Afiliação
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
State University of Minas Gerais. Divinopolis, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Genetics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Animal Science and Food Engineering. University of São Paulo. Pirassununga, SP, Brazil.
Department of Dermatology. University of Wisconsin-Madison. Madison, WI, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Department of Genetics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Institute of Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Resumo em Inglês
A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.
Palavras-chave em inglês
Animals
COVID-19
DNA B-Form
Nanovaccines
SARS-CoV-2
Vaccines DNA
 
Editor
Nature Pub. Group
Referência
GUIMARÃES, Lays Cordeiro et al. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models. Nature Communications, v. 15, n. 1, p. 1-19, Jan. 2024.
DOI
10.1038/s41467-024-44830-1
ISSN
2041-1723