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J Control Release. 2015 Jul 28;210:208-16. doi: 10.1016/j.jconrel.2015.05.278. Epub 2015 May 21.

Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection.

Author information

1
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Animal and Plant Quarantine Agency, 175 Anyangro, Anyang, Gyeonggido 430-757, South Korea.
2
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
3
Department of Chemical and Materials Engineering, University of Alberta, AB T6G 2M9, Canada.
4
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
5
BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggido, South Korea.
6
National Institute of Biological Resources, Incheon 404-708, South Korea.
7
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: skang24@gsu.edu.

Abstract

A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.

KEYWORDS:

Cross-protection; Influenza universal vaccine; M2e5x VLPs; Microneedles

PMID:
26003039
PMCID:
PMC4489561
DOI:
10.1016/j.jconrel.2015.05.278
[Indexed for MEDLINE]
Free PMC Article

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