title: Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.
abstract: Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: John B
authors.initials: JB
authors.lastname: Carey
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Anto
authors.initials: A
authors.lastname: Vrdoljak
authors.affiliation: The Tyndall National Institute, University College Cork, Cork, Ireland.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.affiliation: 1] School of Pharmacy, University College Cork, Cork, Ireland [2] Dept. of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D010967:Plasmodium yoelii / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000914:Antibodies, Viral; D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D017780:Malaria Vaccines