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

Coffey, Jacob w. ; Van der burg, Nicole m. d. LU orcid ; Rananakomol, Thippayawan ; Ng, Hwee-Ing ; Fernando, Germain j. p. and Kendall, Mark a. f. (2022) In Advanced NanoBiomed Research 2(8).
Abstract
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)... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Advanced NanoBiomed Research
volume
2
issue
8
publisher
Wiley
external identifiers
  • scopus:85139416211
ISSN
2699-9307
DOI
10.1002/anbr.202100151
language
English
LU publication?
no
id
42e10f25-3684-4229-90bb-e0b3219867c2
alternative location
https://onlinelibrary.wiley.com/doi/10.1002/anbr.202100151
date added to LUP
2023-11-28 10:45:20
date last changed
2023-11-29 04:11:30
@article{42e10f25-3684-4229-90bb-e0b3219867c2,
  abstract     = {{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.}},
  author       = {{Coffey, Jacob w. and Van der burg, Nicole m. d. and Rananakomol, Thippayawan and Ng, Hwee-Ing and Fernando, Germain j. p. and Kendall, Mark a. f.}},
  issn         = {{2699-9307}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  publisher    = {{Wiley}},
  series       = {{Advanced NanoBiomed Research}},
  title        = {{An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses}},
  url          = {{http://dx.doi.org/10.1002/anbr.202100151}},
  doi          = {{10.1002/anbr.202100151}},
  volume       = {{2}},
  year         = {{2022}},
}