Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
-
Published:2024-01-18
Issue:1
Volume:15
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Guimaraes Lays CordeiroORCID, Costa Pedro Augusto CarvalhoORCID, Scalzo Júnior Sérgio Ricardo AluottoORCID, Ferreira Heloísa Athaydes SeabraORCID, Braga Ana Carolina SoaresORCID, de Oliveira Leonardo Camilo, Figueiredo Maria Marta, Shepherd Sarah, Hamilton AlexORCID, Queiroz-Junior Celso Martins, da Silva Walison NunesORCID, da Silva Natália Jordana AlvesORCID, Rodrigues Alves Marco Túllio, Santos Anderson Kenedy, de Faria Kevin Kelton SantosORCID, Marim Fernanda Martins, Fukumasu Heidge, Birbrair AlexanderORCID, Teixeira-Carvalho Andréa, de Aguiar Renato SantanaORCID, Mitchell Michael J.ORCID, Teixeira Mauro Martins, Vasconcelos Costa Vivian, Frezard FredericORCID, Guimaraes Pedro Pires GoulartORCID
Abstract
AbstractA 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference54 articles.
1. Carabelli, A. M. et al. SARS-CoV-2 variant biology: immune escape, transmission and fitness. Nat. Rev. Microbiol. 21, 162–177 (2023). 2. CRC, J. H. C. R. C. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). University & Medicine. https://coronavirus.jhu.edu/map.html (2023). 3. Lythgoe, M. P. & Middleton, P. Comparison of COVID-19 vaccine approvals at the US food and drug administration, european medicines agency, and Health Canada. JAMA Netw. Open 4, e2114531 (2021). 4. Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021). 5. Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
|
|