An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses

Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which...

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Main Authors: Jacob W. Coffey, Nicole M. D. van der Burg, Thippayawan Rananakomol, Hwee-Ing Ng, Germain J. P. Fernando, Mark A. F. Kendall
Format: Article
Language:English
Published: Wiley-VCH 2022-08-01
Series:Advanced NanoBiomed Research
Subjects:
Online Access:https://doi.org/10.1002/anbr.202100151
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author Jacob W. Coffey
Nicole M. D. van der Burg
Thippayawan Rananakomol
Hwee-Ing Ng
Germain J. P. Fernando
Mark A. F. Kendall
author_facet Jacob W. Coffey
Nicole M. D. van der Burg
Thippayawan Rananakomol
Hwee-Ing Ng
Germain J. P. Fernando
Mark A. F. Kendall
author_sort Jacob W. Coffey
collection DOAJ
description Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion depth, delivery energy/velocity, MN shape, and density. However, these effects have not been systematically investigated. Herein, the effect of MN density on antibody responses to influenza vaccination is assessed, keeping all other variables constant. MN arrays are manufactured within the “high‐density range” from 5 k microneedles cm−2 (n cm−2) to the “ultrahigh” 30 k n cm−2. Prior to this study, the highest MN density used for vaccination is 20 k n cm−2. Thus, MN array vaccination is evaluated over an unprecedented range. Cell viability is assessed in the skin after application and antibody responses at days 21/63. It is demonstrated that increasing MN density from 5 to 30 k n cm−2 increases both epidermal cell death and anti‐influenza IgG1, without an increase in anti‐influenza IgG2a. This suggests that MN density has a direct adjuvant effect on immune responses through Th2‐mediated signalling—a response critical for human vaccination.
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spelling doaj.art-c1b1cfcd169e43cba45a1a892c3690cb2022-12-22T03:43:36ZengWiley-VCHAdvanced NanoBiomed Research2699-93072022-08-0128n/an/a10.1002/anbr.202100151An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune ResponsesJacob W. Coffey0Nicole M. D. van der Burg1Thippayawan Rananakomol2Hwee-Ing Ng3Germain J. P. Fernando4Mark A. F. Kendall5The Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaThe Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaThe Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaThe Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaThe Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaThe Delivery of Drugs and Genes Group (D2G) Australian Institute for Bioengineering and Nanotechnology University of Queensland St. Lucia QLD 4072 AustraliaMany types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion depth, delivery energy/velocity, MN shape, and density. However, these effects have not been systematically investigated. Herein, the effect of MN density on antibody responses to influenza vaccination is assessed, keeping all other variables constant. MN arrays are manufactured within the “high‐density range” from 5 k microneedles cm−2 (n cm−2) to the “ultrahigh” 30 k n cm−2. Prior to this study, the highest MN density used for vaccination is 20 k n cm−2. Thus, MN array vaccination is evaluated over an unprecedented range. Cell viability is assessed in the skin after application and antibody responses at days 21/63. It is demonstrated that increasing MN density from 5 to 30 k n cm−2 increases both epidermal cell death and anti‐influenza IgG1, without an increase in anti‐influenza IgG2a. This suggests that MN density has a direct adjuvant effect on immune responses through Th2‐mediated signalling—a response critical for human vaccination.https://doi.org/10.1002/anbr.202100151adjuvantantibody IgGcell deathdensitymicroneedlesskin vaccination
spellingShingle Jacob W. Coffey
Nicole M. D. van der Burg
Thippayawan Rananakomol
Hwee-Ing Ng
Germain J. P. Fernando
Mark A. F. Kendall
An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
Advanced NanoBiomed Research
adjuvant
antibody IgG
cell death
density
microneedles
skin vaccination
title An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
title_full An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
title_fullStr An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
title_full_unstemmed An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
title_short An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses
title_sort ultrahigh density microneedle array for skin vaccination inducing epidermal cell death by increasing microneedle density enhances total igg and igg1 immune responses
topic adjuvant
antibody IgG
cell death
density
microneedles
skin vaccination
url https://doi.org/10.1002/anbr.202100151
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