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

Background. This study evaluated dissolvable microneedle patch (dMNP) delivery of hepatitis B vaccine in rhesus macaques and provides evidence that dMNP delivery elicits seroprotective anti-HBs levels comparable with human seroprotection, potentially useful for hepatitis B birth dose vaccination in resource-constrained regions. Methods. Sixteen macaques were each vaccinated twice; they were treated in 4 groups, with dMNP delivery of AFV at 24 8 mu g (n = 4) or 48 14 mu g (n = 4), intramuscular injection of AFV (10 mu g; n = 4), or intramuscular injection of AAV (10 mu g; n = 4). Levels of antibody to hepatitis B surface antigen (HBsAg) (anti-HBs) 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, interferon gamma, interleukin 2, and interleukin 4 production by HBsAg-specific T cells was detected. A statistically significant positive correlation was detected between anti-HBs levels and cells producing HBsAg-specific interferon gamma and interleukin 2 (T-helper 1-type cytokine) and interleukin 4 (T-helper 2-type cytokine) in all anti-HBs-positive animals. Conclusions. dMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that are correlated with human seroprotection, and it could be particularly promising for birth dose delivery of hepatitis B vaccine in resource-constrained regions.