TY - JOUR
T1 - Cutaneous vaccination with coated microneedles prevents development of airway allergy
AU - Shakya, Akhilesh Kumar
AU - Lee, Chang Hyun
AU - Gill, Harvinder Singh
N1 - Funding Information:
This research was supported by the National Institutes of Health (NIH) [grant number 1R01AI121322-01 ]. We would like to thank Dr. Erwin W. Gelfand, MD, Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO for advice in establishing the mouse model of ovalbumin-induced airway allergy.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/11/10
Y1 - 2017/11/10
N2 - Allergy cases are increasing worldwide. Currently allergies are treated after their appearance in patients. However, now there is effort to make a preventive vaccine against allergies. The rationale is to target patient populations that are already sensitized to allergens but have yet to develop severe forms of the allergic disease, or who are susceptible to allergy development but have not yet developed them. Subcutaneous injections and the sublingual route have been used as the primary mode of preventive vaccine delivery. However, injections are painful, especially considering that they have to be given repeatedly to infants or young children. The sublingual route is hard to use since infants can't be trained to hold the vaccine under their tongue. In the present study, we demonstrate a microneedle (MN)-based cutaneous preventive allergy treatment against ovalbumin (Ova)-induced airway allergy in mice. Insertion of MNs coated with Ova as a model allergen and CpG oligonucleotide as an adjuvant (MNs-CIT) into the skin significantly induced Ova specific systemic immune response. This response was similar to that induced by hypodermic-needle-based delivery of Ova using the clinically-approved subcutaneous immunotherapy (SCIT) route. MNs-CIT regulated Th2 cytokines (IL-4, IL-5 & IL-13) and anti-inflammatory cytokines (IL-10) in the bronchoalveolar fluid, and IL-2 and IFN-γ cytokines in restimulated splenocyte cultures. Absence of mucus deposition inside the bronchiole wall and low collagen around the lung bronchioles after Ova-allergen challenge further confirmed the protective role of MNs-CIT. Overall, MNs-CIT represents a novel minimally invasive cutaneous immunotherapy to prevent the progression of Ova induced airway allergy in mice.
AB - Allergy cases are increasing worldwide. Currently allergies are treated after their appearance in patients. However, now there is effort to make a preventive vaccine against allergies. The rationale is to target patient populations that are already sensitized to allergens but have yet to develop severe forms of the allergic disease, or who are susceptible to allergy development but have not yet developed them. Subcutaneous injections and the sublingual route have been used as the primary mode of preventive vaccine delivery. However, injections are painful, especially considering that they have to be given repeatedly to infants or young children. The sublingual route is hard to use since infants can't be trained to hold the vaccine under their tongue. In the present study, we demonstrate a microneedle (MN)-based cutaneous preventive allergy treatment against ovalbumin (Ova)-induced airway allergy in mice. Insertion of MNs coated with Ova as a model allergen and CpG oligonucleotide as an adjuvant (MNs-CIT) into the skin significantly induced Ova specific systemic immune response. This response was similar to that induced by hypodermic-needle-based delivery of Ova using the clinically-approved subcutaneous immunotherapy (SCIT) route. MNs-CIT regulated Th2 cytokines (IL-4, IL-5 & IL-13) and anti-inflammatory cytokines (IL-10) in the bronchoalveolar fluid, and IL-2 and IFN-γ cytokines in restimulated splenocyte cultures. Absence of mucus deposition inside the bronchiole wall and low collagen around the lung bronchioles after Ova-allergen challenge further confirmed the protective role of MNs-CIT. Overall, MNs-CIT represents a novel minimally invasive cutaneous immunotherapy to prevent the progression of Ova induced airway allergy in mice.
KW - Airway allergy
KW - Microneedles
KW - Preventive allergy vaccine
KW - Subcutaneous allergy immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=85028344636&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2017.08.012
DO - 10.1016/j.jconrel.2017.08.012
M3 - Article
C2 - 28821461
AN - SCOPUS:85028344636
VL - 265
SP - 75
EP - 82
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -