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J Drug Target. 2016 Dec;24(10):943-951. doi: 10.3109/1061186X.2016.1159213. Epub 2016 Mar 27.

Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

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a Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon, Korea.
b Department of Biomedical Science, Graduate School, Kyung Hee University , Seoul, Korea.
c Department of Medical Zoology, Kyung Hee University School of Medicine , Seoul, Korea.
d Department of Chemical and Materials Engineering, University of Alberta , Edmonton, Alberta, Canada.
e Department of Biochemistry, Dongguk University College of Medicine , Gyeongju, Korea.
f Department of Pathology, Kyung Hee University Medical Center , Seoul, Korea.


A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (pā€‰<ā€‰0.05) reduced. All mice survived after viral challenges. These results indicate that skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.


Influenza; microneedle; protection; trivalent vaccine

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