A Dissolvable Microneedle Formulation of Bordetella pertussis Subunit Vaccine: Translational Development and Immunological Evaluation in Mice

Dan Dan Zhu, Xiao Li Wang, Xiao Peng Zhang, Jing Jing Ma, De Ling Kong, Ming Ming Zhang, Xin Dong Guo, Chun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

This study evaluated the feasibility of microneedle (MN) technology as an alternative approach for pertussis toxin (PT) vaccine delivery. The characterization of PT vaccine MNs ensured sufficient mechanical property to deliver antigens to intradermal tissues of mice for intensive stimulations at the targeting of immune cells. The histological examination suggested that PT vaccine MNs successfully embedded into the mouse dermis to a depth of approximately 330 μm. The in vivo fluorescence imaging showed the sustained and longer release of antigens through MN patches compared to a direct subcutaneous (s.c.) injection, thus resulting in the quick generation of a high level of PT-specific IgG after the first immunization. Moreover, similar IgG levels could be elicited by these two delivery strategies, while less PT antigens were needed using MN patches. The cytokines studies illustrated that PT vaccine MNs could elicit immune responses through multiple pathways, especially of Th1 and Th17 pathways. By integrating the above results, we concluded that the PT MN transdermal drug delivery system could improve antigen utilization and induce rapid and robust PT-specific immune responses, which possessed the superiority over the traditional s.c. injection.

Original languageEnglish (US)
Pages (from-to)5053-5061
Number of pages9
JournalACS Applied Bio Materials
Volume2
Issue number11
DOIs
StatePublished - Nov 18 2019

Bibliographical note

Funding Information:
This work was financially supported by the National Natural Science Foundation of China (51673019, 51873015, and 31600743), the Fundamental Research Funds for the Central Universities and Research projects on biomedical transformation of China-Japan Friendship Hospital (PYBZ1817), the long-term subsidy mechanism from the Ministry of Finance and the Ministry of Education of PRC, and Natural Science Foundation of Tianjin (17JCYBJC29100). All animal studies were conducted in accordance with the guidelines of the Ethics Committee of Beijing University of Chemical Technology, Beijing, China.

Keywords

  • Bordetella pertussis
  • adjuvant
  • antigen delivery
  • formulation
  • humoral immune response
  • microneedle

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