Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

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

2024; Nature Portfolio; Volume: 15; Issue: 1 Linguagem: Inglês

10.1038/s41467-024-44830-1

2041-1723

Lays Cordeiro Guimarães, Pedro Augusto Carvalho Costa, Sérgio Scalzo, Heloísa Athaydes Seabra Ferreira, Ana Carolina Soares Braga, Leonardo Camilo de Oliveira, Maria Marta Figueiredo, Sarah J. Shepherd, Alex G. Hamilton, Celso Martins Queiroz‐Junior, Walison N. Silva, Natália Jordana Alves da Silva, Marco Túllio Rodrigues Alves, Anderson K. Santos, Kevin Kelton Santos de Faria, Fernanda Martins Marim, Heidge Fukumasu, Alexander Birbrair, Andréa Teixeira−Carvalho, Renato Santana Aguiar, Michael J. Mitchell, Mauro Martins Teixeira, Vivian Vasconcelos Costa, Frédéric Frézard, Pedro Pires Goulart Guimarães,

RNA Interference and Gene Delivery

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.