Hepatitis B vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques.

• Type of Material: Article
• Authors: Monica B. Perez Cuevas, Georgia Institute of Technology; Maja Kodani, Centers for Disease Control and Prevention; Youkyung Choi, Centers for Disease Control and Prevention; Jessica Joyce, Georgia Institute of Technology; Siobhan M. O'Connor, Centers for Disease Control and Prevention; Saleem Kamili, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention Centers for Disease Control and Prevention Atlanta GA 30329.; Mark Prausnitz, Emory University
• Language: English
• Date: 2018-09
• Publisher: Wiley Open Access
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Bioengineering & Translational Medicine is published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/btm2.10098
• Title of Journal or Parent Work: Bioengineering and Translational Medicine
• ISSN: 2380-6761
• Volume: 3
• Issue: 3
• Start Page: 186
• End Page: 196
• Grant/Funding Information: NIH/NIGMS‐sponsored cell and Tissue Engineering (CTEng) Biotechnology Training Program (T32‐Gm008433); internal CDC funding; National Science Foundation, DGE‐1650044
• Keywords: microneedle patch; birth dose; hepatitis B virus; rhesus macaque; vaccination; mouse; biomechanics; hepatitis B surface antigen vaccine
• Research Categories: Engineering, Biomedical

Abstract

Chronic Hepatitis B virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. Perinatal and early childhood infections are strongly associated with developing chronic hepatitis B. Adding a birth dose of the hepatitis B vaccine (HepB BD) to routine childhood vaccination can prevent over 85% of these infections. However, HepB BD coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited HepB BD supply at birth. To address the challenges, we developed coated metal microneedle patches (cMNPs) and dissolvable microneedle patches (dMNPs) that deliver adjuvant-free hepatitis B vaccine to the skin in a simple-to-administer manner. The dMNP contains micron-scale, solid needles encapsulating vaccine antigen and dissolve in the skin, generating no sharps waste. We delivered HepB BD via cMNP to BALB/c mice and via dMNP to both mice and rhesus macaques. Both cMNP and dMNP were immunogenic, generating hepatitis B surface antibody levels similar to human seroprotection. Biomechanical analysis showed that at high forces the microneedles failed mechanically by yielding but microneedles partially blunted by axial compression were still able to penetrate skin. Overall, this study indicates that with further development, dMNPs could offer a method of vaccination to increase HepB BD access and reduce needle waste in developing countries.