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

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.

Mother‐to‐child transmission of hepatitis B: What more needs to be done to eliminate it around the world?

“…Recently, 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 have been developed and positively assessed in mice. This technology is still under development and not yet assessed in humans …”

Phage display as a tool for vaccine and immunotherapy development

“…Despite this burden, it is an extremely important vaccination as hepatitis B is highly contagious and leads to approximately 780,000 deaths each year. 76…”

“…This is a highly researched field because of the annual public health burden is actually subject to antigenic drift where mutations occur specifically in antibody-binding sites, resulting in a need to manufacture new vaccines for flu season each year. Despite this burden, it is an extremely important vaccination as hepatitis B is highly contagious and leads to approximately 780,000 deaths each year 76. Despite some success, M2e on its own is poorly immunogenic, likely because it is not highly expressed.…”

Bioengineering & Translational Medicine: Year 2020 in review

“…Indeed, some of the recent BioTM papers in drug delivery have focused on the use of microneedles for vaccine delivery. [1][2][3] These papers demonstrated novel microneedle designs, for example, self-healing microneedles for encapsulation, as well as translational studies to nonhuman primate studies for hepatitis B vaccine. Along the same general theme, studies on ocular drug delivery devices were also featured prominently.…”