Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release
Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. How...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/126811 |
| _version_ | 1811074715120304128 |
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| author | Tzeng, Stephany Y. Guarecuco, Rohiverth McHugh, Kevin J Rose, Sviatlana Rosenberg, Evan Zeng, Yingying Langer, Robert Jaklenec, Ana |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Tzeng, Stephany Y. Guarecuco, Rohiverth McHugh, Kevin J Rose, Sviatlana Rosenberg, Evan Zeng, Yingying Langer, Robert Jaklenec, Ana |
| author_sort | Tzeng, Stephany Y. |
| collection | MIT |
| description | Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50 mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50 mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health. |
| first_indexed | 2024-09-23T09:54:13Z |
| format | Article |
| id | mit-1721.1/126811 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:54:13Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1268112022-09-30T17:37:09Z Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release Tzeng, Stephany Y. Guarecuco, Rohiverth McHugh, Kevin J Rose, Sviatlana Rosenberg, Evan Zeng, Yingying Langer, Robert Jaklenec, Ana Koch Institute for Integrative Cancer Research at MIT Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50 mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50 mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health. Bill & Melinda Gates Foundation (OPP1095790) 2020-08-26T13:55:28Z 2020-08-26T13:55:28Z 2016-05 2016-05 2019-09-06T17:32:13Z Article http://purl.org/eprint/type/JournalArticle 0168-3659 1873-4995 https://hdl.handle.net/1721.1/126811 Tzeng, Stephany Y., Rohiverth Guarecuco, Kevin J. McHugh et al. "Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release." Journal of Controlled Release 233, July 2016:p.101-113. © 2016 The Authors. en https://dx.doi.org/10.1016/J.JCONREL.2016.05.012 Journal of Controlled Release Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Tzeng, Stephany Y. Guarecuco, Rohiverth McHugh, Kevin J Rose, Sviatlana Rosenberg, Evan Zeng, Yingying Langer, Robert Jaklenec, Ana Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title | Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title_full | Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title_fullStr | Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title_full_unstemmed | Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title_short | Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release |
| title_sort | thermostabilization of inactivated polio vaccine in plga based microspheres for pulsatile release |
| url | https://hdl.handle.net/1721.1/126811 |
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