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

Manon L M Prins; Corine Prins; Jutte J C de Vries; Leo G Visser; Anna H E Roukens

doi:10.1016/j.virusres.2023.199175

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 Res. 2023 Sep:334:199175. doi: 10.1016/j.virusres.2023.199175. Epub 2023 Jul 21.

Authors

Manon L M Prins¹, Corine Prins², Jutte J C de Vries³, Leo G Visser², Anna H E Roukens²

Affiliations

¹ Department of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the Netherlands. Electronic address: m.l.m.prins@lumc.nl.
² Department of Infectious Diseases, Leiden University Medical Centre, C5-P Albinusdreef 2, Leiden, ZA 2333, the Netherlands.
³ Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands.

Abstract

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.

Keywords: COVID-19; Ceramic skin patch; Dose-sparing; Immunogenicity; Safety; mRNA-1273 vaccine.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

2019-nCoV Vaccine mRNA-1273* / administration & dosage
2019-nCoV Vaccine mRNA-1273* / adverse effects
2019-nCoV Vaccine mRNA-1273* / chemistry
2019-nCoV Vaccine mRNA-1273* / immunology
Administration, Cutaneous
Adult
Antibody Formation
COVID-19* / immunology
COVID-19* / prevention & control
Female
Humans
Male
Middle Aged
Young Adult

Substances

2019-nCoV Vaccine mRNA-1273
PittCoVacc
Lipid Nanoparticles

Associated data

ClinicalTrials.gov/NCT05315362