Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2.
Ria LassaunièreCharlotta PolacekGregers J GramAnders FrischeJeanette Linnea TingstedtMaren KrügerBrigitte Gertrud DornerAnthony CookRenita BrownTatyana OrekovTammy Putmon-TaylorTracey-Ann CampbellJack GreenhouseLaurent PessaintHanne A ElyardMark G LewisAnders FomsgaardPublished in: NPJ vaccines (2021)
New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- circulating tumor
- cell free
- single molecule
- escherichia coli
- clinical trial
- immune response
- public health
- crispr cas
- emergency department
- stem cells
- coronavirus disease
- randomized controlled trial
- small molecule
- insulin resistance
- circulating tumor cells
- inflammatory response
- metabolic syndrome
- oxidative stress
- toll like receptor
- adipose tissue
- high throughput
- cell therapy
- protein protein
- mesenchymal stem cells
- drug induced
- stress induced
- dna binding
- study protocol
- binding protein