Local Sustained GM-CSF Delivery by Genetically Engineered Encapsulated Cells Enhanced Both Cellular and Humoral SARS-CoV-2 Spike-Specific Immune Response in an Experimental Murine Spike DNA Vaccination Model
| Autor: | Nicolas Mach, Ugo Tomasello, Rémi Vernet, Sabine Fievre, Erika Cosset, Emily Charrier, Julien Grogg |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DNA vaccine
medicine.medical_treatment 030231 tropical medicine Immunology Biology Virus Article DNA vaccination 03 medical and health sciences 0302 clinical medicine Immune system adjuvant Viral entry Drug Discovery SARS-CoV-2 COVID 19 GM-CSF medicine Pharmacology (medical) 030212 general & internal medicine ddc:616 Pharmacology Acquired immune system ddc:616.8 Vaccination Infectious Diseases Immunization Medicine Adjuvant |
| Zdroj: | Vaccines; Volume 9; Issue 5; Pages: 484 Vaccines Vaccines, Vol. 9, No 5 (2021) P. 484 Vaccines, Vol 9, Iss 484, p 484 (2021) |
| ISSN: | 2076-393X |
| DOI: | 10.3390/vaccines9050484 |
| Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with recurrences. Therefore, finding a vaccine for this virus became a priority for the scientific community. The SARS-CoV-2 spike protein has been described as the keystone for viral entry into cells and effective immune protection against SARS-CoV-2 is elicited by this protein. Consequently, many commercialized vaccines focus on the spike protein and require the use of an optimal adjuvant during vaccination. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated a powerful enhancement of acquired immunity against many pathogens when delivered in a sustained and local manner. In this context, we developed an encapsulated cell-based technology consisting of a biocompatible, semipermeable capsule for secretion of GM-CSF. In this study, we investigated whether murine GM-CSF (muGM-CSF) represents a suitable adjuvant for SARS-CoV-2 immunization, and which delivery strategy for muGM-CSF could be most beneficial. To test this, different groups of mice were immunized with intra-dermal (i.d.) electroporated spike DNA in the absence or presence of recombinant or secreted muGM-CSF. Results demonstrated that adjuvanting a spike DNA vaccine with secreted muGM-CSF resulted in enhancement of specific cellular and humoral immune responses against SARS-CoV-2. Our data also highlighted the importance of delivery strategies to the induction of cellular and humoral-mediated responses. |
| Databáze: | OpenAIRE |
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