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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Main Authors: Keegan Braz Gomes, Sharon Vijayanand, Priyal Bagwe, Ipshita Menon, Akanksha Kale, Smital Patil, Sang-Moo Kang, Mohammad N. Uddin, Martin J. D’Souza
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10612
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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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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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