Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling

Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibili...

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Main Authors: In-Jeong Choi, Hye-Ran Cha, Su Jin Hwang, Seung-Ki Baek, Jae Myun Lee, Seong-O Choi
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/13/2/209
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author In-Jeong Choi
Hye-Ran Cha
Su Jin Hwang
Seung-Ki Baek
Jae Myun Lee
Seong-O Choi
author_facet In-Jeong Choi
Hye-Ran Cha
Su Jin Hwang
Seung-Ki Baek
Jae Myun Lee
Seong-O Choi
author_sort In-Jeong Choi
collection DOAJ
description Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.
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spelling doaj.art-45a4911a08ff40f0a02665c67729b9082023-12-03T12:15:06ZengMDPI AGPharmaceutics1999-49232021-02-0113220910.3390/pharmaceutics13020209Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and StockpilingIn-Jeong Choi0Hye-Ran Cha1Su Jin Hwang2Seung-Ki Baek3Jae Myun Lee4Seong-O Choi5QuadMedicine R&D Centre, QuadMedicine, Inc., Seongnam 13209, KoreaDepartment of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, KoreaQuadMedicine R&D Centre, QuadMedicine, Inc., Seongnam 13209, KoreaDepartment of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, KoreaQuadMedicine R&D Centre, QuadMedicine, Inc., Seongnam 13209, KoreaAlthough smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At −20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.https://www.mdpi.com/1999-4923/13/2/209smallpoxmicroneedlevaccinia viruscoatingstabilityimmune response
spellingShingle In-Jeong Choi
Hye-Ran Cha
Su Jin Hwang
Seung-Ki Baek
Jae Myun Lee
Seong-O Choi
Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
Pharmaceutics
smallpox
microneedle
vaccinia virus
coating
stability
immune response
title Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
title_full Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
title_fullStr Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
title_full_unstemmed Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
title_short Live Vaccinia Virus-Coated Microneedle Array Patches for Smallpox Vaccination and Stockpiling
title_sort live vaccinia virus coated microneedle array patches for smallpox vaccination and stockpiling
topic smallpox
microneedle
vaccinia virus
coating
stability
immune response
url https://www.mdpi.com/1999-4923/13/2/209
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