Feasibility of Hepatitis B Vaccination by Microneedle Patch: Cellular and Humoral Immunity Studies in Rhesus Macaques

BACKGROUND Dissolvable microneedle patches (dMNPs) provide ease of deployment and eliminate need for hypodermic needle disposal after conventional vaccinations. In this study, immunogenicity of dMNP delivery of adjuvant-free monovalent hepatitis B surface antigen (HBsAg) vaccine (AFV) to standard intramuscular (IM) injection of monovalent aluminum-adjuvanted monovalent hepatitis B vaccine (AAV) were compared in rhesus macaques. METHODS Sixteen macaques were immunized twice in 4 groups: dMNP delivery of 24 ± 8µg (n=4) or 48 ± 14µg (n=4) AFV; IM injection of 10µg AFV (IM AFV, n=4); and IM injection of 10µg AAV (IM AAV, n=4). Levels of hepatitis B surface antibody and HBsAg-specific T-cell responses were analyzed. RESULTS Six of 8 animals with dMNP delivery of AFV had anti-HBs levels ≥10 mIU/ml after the first vaccine dose. After dMNP delivery of AFV, IFN-γ, IL-2, and IL-4 production by HBsAg-specific T-cells were detected. A statistically significant positive correlation was detected between anti-HBs levels and HBsAg-specific IFN-γ and IL-2 (Th1-type cytokine) and IL-4 (Th2-type cytokine) producing cells in all anti-HBs positive animals. CONCLUSIONS dMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that correlate in human seroprotection, and could be particularly promising for hepatitis B vaccine birth dose delivery in resource-constrained regions.