Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models

Lays Cordeiro Guimaraes, Pedro Augusto Carvalho Costa, Sérgio Ricardo Aluotto Scalzo Júnior, Heloísa Athaydes Seabra Ferreira, Ana Carolina Soares Braga, Leonardo Camilo Oliveira, Maria Marta Figueiredo, Sarah Shepherd, Alex Hamilton, Celso Martins Queiroz-Junior, Walison Nunes Silva, Natália Jordana Alves da Silva, Marco Túllio Rodrigues Alves, Anderson Kenedy Santos, Kevin Kelton Santos Faria, Fernanda Martins Marim, Heidge Fukumasu, Alexander Birbrair, Andréa Teixeira-Carvalho, Renato Santana Aguiar, Michael J. Mitchell, Mauro Martins Teixeira, Vivian Vasconcelos Costa, Frederic Frezard and Pedro Pires Goulart Guimaraes ()
Additional contact information
Lays Cordeiro Guimaraes: Federal University of Minas Gerais
Pedro Augusto Carvalho Costa: Federal University of Minas Gerais
Sérgio Ricardo Aluotto Scalzo Júnior: Federal University of Minas Gerais
Heloísa Athaydes Seabra Ferreira: Federal University of Minas Gerais
Ana Carolina Soares Braga: Federal University of Minas Gerais
Leonardo Camilo Oliveira: Federal University of Minas Gerais
Maria Marta Figueiredo: State University of Minas Gerais
Sarah Shepherd: University of Pennsylvania
Alex Hamilton: University of Pennsylvania
Celso Martins Queiroz-Junior: Federal University of Minas Gerais
Walison Nunes Silva: Federal University of Minas Gerais
Natália Jordana Alves da Silva: Federal University of Minas Gerais
Marco Túllio Rodrigues Alves: Federal University of Minas Gerais
Anderson Kenedy Santos: Federal University of Minas Gerais
Kevin Kelton Santos Faria: Federal University of Minas Gerais
Fernanda Martins Marim: Federal University of Minas Gerais
Heidge Fukumasu: University of São Paulo
Alexander Birbrair: University of Wisconsin-Madison
Andréa Teixeira-Carvalho: Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz
Renato Santana Aguiar: Federal University of Minas Gerais
Michael J. Mitchell: University of Pennsylvania
Mauro Martins Teixeira: Federal University of Minas Gerais
Vivian Vasconcelos Costa: Federal University of Minas Gerais
Frederic Frezard: Federal University of Minas Gerais
Pedro Pires Goulart Guimaraes: Federal University of Minas Gerais

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-44830-1

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