Cross-protection by co-immunization with influenza hemagglutinin DNA and inactivated virus vaccine using coated microneedles

• Type of Material: Article
• Authors: Yeu-Chun Kim, Korea Advanced Institute of Science and Technology; Dae-Goon Yoo, University of Georgia; Richard W Compans, Emory University; Sang-Moo Kang, Georgia State University; Mark R. Prausnitz, Emory University
• Language: English
• Date: 2013-12-10
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jconrel.2013.04.016
• Title of Journal or Parent Work: Journal of Controlled Release
• ISSN: 0168-3659
• Volume: 172
• Issue: 2
• Start Page: 579
• End Page: 588
• Grant/Funding Information: This work was funded in part by NIH/NIBIB grant EB006369 (M.R.P.); and NIH/NIAID grants AI0680003 (R.W.C.), AI093772 (S.M.K.), AI087782 (S.M.K.), and AI105170 (S.M.K.).
• Keywords: Science & Technology; EFFICACY; Chemistry; Life Sciences & Biomedicine; Influenza virus; Coating; PARTICLE VACCINE; Cross-protection; IMMUNITY; IMMUNOGENICITY; CHALLENGE INFECTION; DELIVERY; Physical Sciences; DNA vaccine; PANDEMIC INFLUENZA; Chemistry, Multidisciplinary; Microneedle; ANTIBODY; SKIN; A VACCINE; Pharmacology & Pharmacy
• Research Categories: Health Sciences, Immunology; Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

The need for annual revaccination against influenza is a burden on the healthcare system, leads to low vaccination rates and makes timely vaccination difficult against pandemic strains, such as during the 2009 H1N1 influenza pandemic. In an effort toward achieving a broadly protective vaccine that provides cross-protection against multiple strains of influenza, this study developed a microneedle patch to co-immunize with A/PR8 influenza hemagglutinin DNA and A/PR8 inactivated virus vaccine. We hypothesize that this dual component vaccination strategy administered to the skin using microneedles will provide cross-protection against other strains of influenza. To test this hypothesis, we developed a novel coating formulation that did not require additional excipients to increase coating solution viscosity by using the DNA vaccine itself to increase viscosity and thereby enable thick coatings of DNA vaccine and inactivated virus vaccine on metal microneedles. Co-immunization in this way not only generated robust antibody responses against A/PR8 influenza but also generated robust heterologous antibody responses against pandemic 2009 H1N1 influenza in mice. Challenge studies showed complete cross-protection against lethal challenge with live pandemic 2009 H1N1 virus. Control experiments using A/PR8 inactivated influenza virus vaccine with placebo DNA coated onto microneedles produced lower antibody titers and provided incomplete protection against challenge. Overall, this is the first study showing DNA solution as a microneedle coating agent and demonstrating cross-protection by co-immunization with inactivated virus and DNA vaccine using coated microneedles.