Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers
Introduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170223001375 |
| _version_ | 1797755785897312256 |
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| author | Manon L.M. Prins Corine Prins Jutte J.C. de Vries Leo G. Visser Anna H.E. Roukens |
| author_facet | Manon L.M. Prins Corine Prins Jutte J.C. de Vries Leo G. Visser Anna H.E. Roukens |
| author_sort | Manon L.M. Prins |
| collection | DOAJ |
| description | Introduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA. Methods: This study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination. Results: In April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA. Conclusion: Needle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov): NCT05315362. |
| first_indexed | 2024-03-12T17:52:12Z |
| format | Article |
| id | doaj.art-0e92cca4188b4c65b4ae418dcb29c192 |
| institution | Directory Open Access Journal |
| issn | 1872-7492 |
| language | English |
| last_indexed | 2024-03-12T17:52:12Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj.art-0e92cca4188b4c65b4ae418dcb29c1922023-08-03T04:22:35ZengElsevierVirus Research1872-74922023-09-01334199175Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteersManon L.M. Prins0Corine Prins1Jutte J.C. de Vries2Leo G. Visser3Anna H.E. Roukens4Department of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the Netherlands; Corresponding author.Department of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the NetherlandsDepartment of Medical Microbiology, Leiden University Medical Centre, Leiden, the NetherlandsDepartment of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the NetherlandsDepartment of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the NetherlandsIntroduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA. Methods: This study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination. Results: In April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA. Conclusion: Needle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov): NCT05315362.http://www.sciencedirect.com/science/article/pii/S0168170223001375COVID-19SafetyImmunogenicitymRNA-1273 vaccineCeramic skin patchDose-sparing |
| spellingShingle | Manon L.M. Prins Corine Prins Jutte J.C. de Vries Leo G. Visser Anna H.E. Roukens Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers Virus Research COVID-19 Safety Immunogenicity mRNA-1273 vaccine Ceramic skin patch Dose-sparing |
| title | Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers |
| title_full | Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers |
| title_fullStr | Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers |
| title_full_unstemmed | Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers |
| title_short | Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers |
| title_sort | establishing immunogenicity and safety of needle free intradermal delivery by nanoporous ceramic skin patch of mrna sars cov 2 vaccine as a revaccination strategy in healthy volunteers |
| topic | COVID-19 Safety Immunogenicity mRNA-1273 vaccine Ceramic skin patch Dose-sparing |
| url | http://www.sciencedirect.com/science/article/pii/S0168170223001375 |
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