Low adenovirus vaccine doses administered to skin using microneedle patches induce better functional antibody immunogenicity as compared to systemic injection

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dc.contributor.authorFlynn, Oliviaen
dc.contributor.authorDillane, Kateen
dc.contributor.authorLanza, Juliane S.en
dc.contributor.authorMarshall, Jennifer M.en
dc.contributor.authorJin, Jingen
dc.contributor.authorSilk, Sarah E.en
dc.contributor.authorDraper, Simon J.en
dc.contributor.authorMoore, Anne C.en
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2024-02-27T12:18:39Z
dc.date.available2024-02-27T12:18:39Z
dc.date.issued2021en
dc.description.abstractAdenovirus-based vaccines are demonstrating promising clinical potential for multiple infectious diseases, including COVID-19. However, the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti-vector neutralizing immunity. Here we determined how dissolvable microneedle patches (DMN) for skin immunization can overcome this issue, using a clinically-relevant adenovirus-based Plasmodium falciparum malaria vaccine, AdHu5–PfRH5, in mice. Incorporation of vaccine into patches significantly enhanced its thermostability compared to the liquid form. Conventional high dose repeated immunization by the intramuscular (IM) route induced low antigen-specific IgG titres and high anti-vector immunity. A low priming dose of vaccine, by the IM route, but more so using DMN patches, induced the most efficacious immune responses, assessed by parasite growth inhibitory activity (GIA) assays. Administration of low dose AdHu5–PfRH5 using patches to the skin, boosted by high dose IM, induced the highest antigen-specific serum IgG response after boosting, the greatest skewing of the antibody response towards the antigen and away from the vector, and the highest efficacy. This study therefore demonstrates that repeated use of the same adenovirus vaccine can be highly immunogenic towards the transgene if a low dose is used to prime the response. It also provides a method of stabilizing adenovirus vaccine, in easy-to-administer dissolvable microneedle patches, permitting storage and distribution out of cold chain.en
dc.description.sponsorshipHealth Research Board (Patient Oriented Research, Grant POR/2012/95)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid299en
dc.identifier.citationFlynn, O., Dillane, K., Lanza, J.S., Marshall, J.M., Jin, J., Silk, S.E., Draper, S.J. and Moore, A.C. (2021) ‘Low adenovirus vaccine doses administered to skin using microneedle patches induce better functional antibody immunogenicity as compared to systemic injection’, Vaccines, 9(3), 299 (17pp). doi: 10.3390/vaccines9030299en
dc.identifier.doi10.3390/vaccines9030299en
dc.identifier.endpage17en
dc.identifier.issn2076-393Xen
dc.identifier.issued3en
dc.identifier.journaltitleVaccinesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/15589
dc.identifier.volume9en
dc.language.isoenen
dc.publisherMDPI AGen
dc.rights© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectAdenovirusen
dc.subjectVirus vector vaccineen
dc.subjectSkinen
dc.subjectDoseen
dc.subjectStabilityen
dc.subjectAntibodyen
dc.subjectAnti-vector immunityen
dc.titleLow adenovirus vaccine doses administered to skin using microneedle patches induce better functional antibody immunogenicity as compared to systemic injectionen
dc.typeArticle (peer-reviewed)en
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