Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles
This study focused on developing an influenza vaccine delivered in polymeric nanoparticles (NPs) using dissolving microneedles. We first formulated an influenza extracellular matrix protein 2 virus-like particle (M2e VLP)-loaded with poly(lactic-co-glycolic) acid (PLGA) nanoparticles, yielding M2e5x...
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MDPI AG
2023-06-01
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author | Keegan Braz Gomes Sharon Vijayanand Priyal Bagwe Ipshita Menon Akanksha Kale Smital Patil Sang-Moo Kang Mohammad N. Uddin Martin J. D’Souza |
author_facet | Keegan Braz Gomes Sharon Vijayanand Priyal Bagwe Ipshita Menon Akanksha Kale Smital Patil Sang-Moo Kang Mohammad N. Uddin Martin J. D’Souza |
author_sort | Keegan Braz Gomes |
collection | DOAJ |
description | This study focused on developing an influenza vaccine delivered in polymeric nanoparticles (NPs) using dissolving microneedles. We first formulated an influenza extracellular matrix protein 2 virus-like particle (M2e VLP)-loaded with poly(lactic-co-glycolic) acid (PLGA) nanoparticles, yielding M2e5x VLP PLGA NPs. The vaccine particles were characterized for their physical properties and in vitro immunogenicity. Next, the M2e5x VLP PLGA NPs, along with the adjuvant Alhydrogel<sup>®</sup> and monophosphoryl lipid A<sup>®</sup> (MPL-A<sup>®</sup>) PLGA NPs, were loaded into fast-dissolving microneedles. The vaccine microneedle patches were then evaluated in vivo in a murine model. The results from this study demonstrated that the vaccine nanoparticles effectively stimulated antigen-presenting cells in vitro resulting in enhanced autophagy, nitric oxide, and antigen presentation. In mice, the vaccine elicited M2e-specific antibodies in both serum and lung supernatants (post-challenge) and induced significant expression of CD4<sup>+</sup> and CD8<sup>+</sup> populations in the lymph nodes and spleens of immunized mice. Hence, this study demonstrated that polymeric particulates for antigen and adjuvant encapsulation, delivered using fast-dissolving microneedles, significantly enhanced the immunogenicity of a conserved influenza antigen. |
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issn | 1661-6596 1422-0067 |
language | English |
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publishDate | 2023-06-01 |
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spelling | doaj.art-76236097e2f6482a9be1f1af907dc4b32023-11-18T16:40:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131061210.3390/ijms241310612Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA NanoparticlesKeegan Braz Gomes0Sharon Vijayanand1Priyal Bagwe2Ipshita Menon3Akanksha Kale4Smital Patil5Sang-Moo Kang6Mohammad N. Uddin7Martin J. D’Souza8Center for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery and Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAThis study focused on developing an influenza vaccine delivered in polymeric nanoparticles (NPs) using dissolving microneedles. We first formulated an influenza extracellular matrix protein 2 virus-like particle (M2e VLP)-loaded with poly(lactic-co-glycolic) acid (PLGA) nanoparticles, yielding M2e5x VLP PLGA NPs. The vaccine particles were characterized for their physical properties and in vitro immunogenicity. Next, the M2e5x VLP PLGA NPs, along with the adjuvant Alhydrogel<sup>®</sup> and monophosphoryl lipid A<sup>®</sup> (MPL-A<sup>®</sup>) PLGA NPs, were loaded into fast-dissolving microneedles. The vaccine microneedle patches were then evaluated in vivo in a murine model. The results from this study demonstrated that the vaccine nanoparticles effectively stimulated antigen-presenting cells in vitro resulting in enhanced autophagy, nitric oxide, and antigen presentation. In mice, the vaccine elicited M2e-specific antibodies in both serum and lung supernatants (post-challenge) and induced significant expression of CD4<sup>+</sup> and CD8<sup>+</sup> populations in the lymph nodes and spleens of immunized mice. Hence, this study demonstrated that polymeric particulates for antigen and adjuvant encapsulation, delivered using fast-dissolving microneedles, significantly enhanced the immunogenicity of a conserved influenza antigen.https://www.mdpi.com/1422-0067/24/13/10612influenzavaccinemicroneedlesnanoparticlesVLPPLGA |
spellingShingle | Keegan Braz Gomes Sharon Vijayanand Priyal Bagwe Ipshita Menon Akanksha Kale Smital Patil Sang-Moo Kang Mohammad N. Uddin Martin J. D’Souza Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles International Journal of Molecular Sciences influenza vaccine microneedles nanoparticles VLP PLGA |
title | Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles |
title_full | Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles |
title_fullStr | Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles |
title_full_unstemmed | Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles |
title_short | Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles |
title_sort | vaccine induced immunity elicited by microneedle delivery of influenza ectodomain matrix protein 2 virus like particle m2e vlp loaded plga nanoparticles |
topic | influenza vaccine microneedles nanoparticles VLP PLGA |
url | https://www.mdpi.com/1422-0067/24/13/10612 |
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