TY - JOUR
T1 - Preclinical study of influenza bivalent vaccine delivered with a two compartmental microneedle array
AU - Jeong, Hye Rin
AU - Bae, Joon Yong
AU - Park, Jee Hyun
AU - Baek, Seung Ki
AU - Kim, Gayeong
AU - Park, Man Seong
AU - Park, Jung Hwan
N1 - Funding Information:
This work was funded by grants from Korea Ministry of Trade, Industry & Energy, South Korea (MOTIE, 10067809 (Industrial Strategic Technology Development Program)). We appreciate Il-Yang Pharmaceutical Co. to provide B/Victoria and B/Yamagata vaccine.
Publisher Copyright:
© 2020 The Authors
PY - 2020/8/10
Y1 - 2020/8/10
N2 - Multiple vaccines can be mixed into a single combination to be a single product. However, combination vaccines have problems of complexity. In this study, microneedles were utilized in a compartmental microneedle array (CMA) to deliver two influenza vaccine strains without mixing. In this study, the CMA had two compartments, and two rectangular structures were attached to each end of the array to enable integration of the compartments with the coating equipment. The coating solution, which contained influenza vaccines for B/Yamagata (B-Y) and B/Victoria (B-V), was filled into the two reservoirs of the container. The CMA was aligned with the container for dipping the first compartment of the array into the first reservoir and the second compartment into the second reservoir. The CMA containing B-Y and B-V separately was administered to mice, and weight change and survival were compared with other groups of mice administered (a) combination vaccines with microneedles, (b) two monovalent vaccines with microneedles, (c) intramuscularly with a combination vaccine, and (d) intramuscularly with two monovalent vaccines. Plaque reduction neutralization tests were also performed to compare the CMA group with the other groups. The CMA showed a relative standard error of less than 7% between samples in dose uniformity. It also showed comparable antibody-forming efficacy compared to other groups, especially by B/Yamagata virus challenge. The CMA mice group showed better survival and weight change than mice that received intramuscular (IM) injection of the combination vaccine. In the neutralizing antibody experiment, all microneedle groups showed a higher neutralizing antibody than the IM groups. Vaccines were administered without mixing by a single administration using a CMA, and the CMA showed comparable efficacy with IM administration of the combination vaccine. Multivalent vaccines can be delivered without mixing as a single product by using a CMA.
AB - Multiple vaccines can be mixed into a single combination to be a single product. However, combination vaccines have problems of complexity. In this study, microneedles were utilized in a compartmental microneedle array (CMA) to deliver two influenza vaccine strains without mixing. In this study, the CMA had two compartments, and two rectangular structures were attached to each end of the array to enable integration of the compartments with the coating equipment. The coating solution, which contained influenza vaccines for B/Yamagata (B-Y) and B/Victoria (B-V), was filled into the two reservoirs of the container. The CMA was aligned with the container for dipping the first compartment of the array into the first reservoir and the second compartment into the second reservoir. The CMA containing B-Y and B-V separately was administered to mice, and weight change and survival were compared with other groups of mice administered (a) combination vaccines with microneedles, (b) two monovalent vaccines with microneedles, (c) intramuscularly with a combination vaccine, and (d) intramuscularly with two monovalent vaccines. Plaque reduction neutralization tests were also performed to compare the CMA group with the other groups. The CMA showed a relative standard error of less than 7% between samples in dose uniformity. It also showed comparable antibody-forming efficacy compared to other groups, especially by B/Yamagata virus challenge. The CMA mice group showed better survival and weight change than mice that received intramuscular (IM) injection of the combination vaccine. In the neutralizing antibody experiment, all microneedle groups showed a higher neutralizing antibody than the IM groups. Vaccines were administered without mixing by a single administration using a CMA, and the CMA showed comparable efficacy with IM administration of the combination vaccine. Multivalent vaccines can be delivered without mixing as a single product by using a CMA.
KW - B/Victoria
KW - B/Yamagata
KW - Bivalent influenza vaccine
KW - Compartmental microneedle array
KW - Influenza
KW - Single administration
UR - http://www.scopus.com/inward/record.url?scp=85085187478&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.05.024
DO - 10.1016/j.jconrel.2020.05.024
M3 - Article
C2 - 32439360
AN - SCOPUS:85085187478
SN - 0168-3659
VL - 324
SP - 280
EP - 288
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -