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

Abstract

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 (p < 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.

Keywords:

• Influenza
• microneedle
• protection
• trivalent vaccine

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding information

This work was supported by a grant from the National Research Foundation of Korea (NRF) (NRF-2014R1A2A2A01004899), a grant from the Agri-Bio Industry Technology Development Program (315030–03-1-HD020), IPET, MAFRA, KHIDI, and a grant from the Ministry of Health & Welfare, Republic of Korea (HI15C2928) and Ministry of Science, ICT, and Future Planning (Project No. NRF-2014M3A9E4064580).