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

• Published in: The Journal of infectious diseases 2019-11, Vol.220 (12), p.1926-1934
• Main Authors: Choi, Youkyung H, Perez-Cuevas, Monica B, Kodani, Maja, Zhang, Xiugen, Prausnitz, Mark R, Kamili, Saleem, O’Connor, Siobhan M
• Format: Article
• Language: English
• Subjects: Animals; Birth; Cytokines; Cytokines - metabolism; Disease Models, Animal; Epitopes, T-Lymphocyte - immunology; Hepatitis; Hepatitis B; Hepatitis B - immunology; Hepatitis B - prevention & control; Hepatitis B Antibodies - immunology; Hepatitis B surface antigen; Hepatitis B Surface Antigens - immunology; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - immunology; Hepatitis B virus - immunology; Humans; Humoral immunity; Immunity, Cellular; Immunity, Humoral; Immunization - methods; Injection; Interferon; Interleukin 2; Interleukin 4; Lymphocytes T; Macaca mulatta; Major and Brief Reports; Statistical analysis; Vaccination; Vaccination - methods; Vaccines; γ-Interferon
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz399

Abstract 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 µg (n = 4) or 48 ± 14 µg (n = 4), intramuscular injection of AFV (10 µg; n = 4), or intramuscular injection of AAV (10 µg; 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 γ, 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 γ 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.