학술논문
Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Document Type
article
Author
Lays Cordeiro Guimaraes; Pedro Augusto Carvalho Costa; Sérgio Ricardo Aluotto Scalzo Júnior; Heloísa Athaydes Seabra Ferreira; Ana Carolina Soares Braga; Leonardo Camilo de Oliveira; Maria Marta Figueiredo; Sarah Shepherd; Alex Hamilton; Celso Martins Queiroz-Junior; Walison Nunes da Silva; Natália Jordana Alves da Silva; Marco Túllio Rodrigues Alves; Anderson Kenedy Santos; Kevin Kelton Santos de Faria; Fernanda Martins Marim; Heidge Fukumasu; Alexander Birbrair; Andréa Teixeira-Carvalho; Renato Santana de Aguiar; Michael J. Mitchell; Mauro Martins Teixeira; Vivian Vasconcelos Costa; Frederic Frezard; Pedro Pires Goulart Guimaraes
Source
Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024)
Subject
Language
English
ISSN
2041-1723
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.