tetano
Editor, Senior Moderator
Nat Commun
. 2024 Jan 18;15(1):590.
doi: 10.1038/s41467-024-44830-1. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Lays Cordeiro Guimaraes[SUP] 1 [/SUP], Pedro Augusto Carvalho Costa[SUP] 1 [/SUP], Sérgio Ricardo Aluotto Scalzo Júnior[SUP] 1 [/SUP], Heloísa Athaydes Seabra Ferreira[SUP] 1 [/SUP], Ana Carolina Soares Braga[SUP] 1 [/SUP], Leonardo Camilo de Oliveira[SUP] 2 [/SUP], Maria Marta Figueiredo[SUP] 3 [/SUP], Sarah Shepherd[SUP] 4 [/SUP], Alex Hamilton[SUP] 4 [/SUP], Celso Martins Queiroz-Junior[SUP] 5 [/SUP], Walison Nunes da Silva[SUP] 1 [/SUP], Natália Jordana Alves da Silva[SUP] 1 [/SUP], Marco Túllio Rodrigues Alves[SUP] 1 [/SUP], Anderson Kenedy Santos[SUP] 1 [/SUP], Kevin Kelton Santos de Faria[SUP] 1 [/SUP], Fernanda Martins Marim[SUP] 6 [/SUP], Heidge Fukumasu[SUP] 7 [/SUP], Alexander Birbrair[SUP] 8 [/SUP], Andréa Teixeira-Carvalho[SUP] 9 [/SUP], Renato Santana de Aguiar[SUP] 6 [/SUP], Michael J Mitchell[SUP] 4 [/SUP], Mauro Martins Teixeira[SUP] 2 [/SUP], Vivian Vasconcelos Costa[SUP] 5 [/SUP], Frederic Frezard[SUP] 1 [/SUP], Pedro Pires Goulart Guimaraes[SUP] 10 [/SUP]
Affiliations
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.
. 2024 Jan 18;15(1):590.
doi: 10.1038/s41467-024-44830-1. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Lays Cordeiro Guimaraes[SUP] 1 [/SUP], Pedro Augusto Carvalho Costa[SUP] 1 [/SUP], Sérgio Ricardo Aluotto Scalzo Júnior[SUP] 1 [/SUP], Heloísa Athaydes Seabra Ferreira[SUP] 1 [/SUP], Ana Carolina Soares Braga[SUP] 1 [/SUP], Leonardo Camilo de Oliveira[SUP] 2 [/SUP], Maria Marta Figueiredo[SUP] 3 [/SUP], Sarah Shepherd[SUP] 4 [/SUP], Alex Hamilton[SUP] 4 [/SUP], Celso Martins Queiroz-Junior[SUP] 5 [/SUP], Walison Nunes da Silva[SUP] 1 [/SUP], Natália Jordana Alves da Silva[SUP] 1 [/SUP], Marco Túllio Rodrigues Alves[SUP] 1 [/SUP], Anderson Kenedy Santos[SUP] 1 [/SUP], Kevin Kelton Santos de Faria[SUP] 1 [/SUP], Fernanda Martins Marim[SUP] 6 [/SUP], Heidge Fukumasu[SUP] 7 [/SUP], Alexander Birbrair[SUP] 8 [/SUP], Andréa Teixeira-Carvalho[SUP] 9 [/SUP], Renato Santana de Aguiar[SUP] 6 [/SUP], Michael J Mitchell[SUP] 4 [/SUP], Mauro Martins Teixeira[SUP] 2 [/SUP], Vivian Vasconcelos Costa[SUP] 5 [/SUP], Frederic Frezard[SUP] 1 [/SUP], Pedro Pires Goulart Guimaraes[SUP] 10 [/SUP]
Affiliations
- PMID: 38238326
- PMCID: PMC10796936
- DOI: 10.1038/s41467-024-44830-1
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.