Abstract
It is a high priority to develop a simple and effective delivery method for a cross-protective influenza vaccine. We investigated skin immunization by microneedle (MN) patch with human influenza split vaccine and virus-like particles containing heterologous M2 extracellular (M2e) domains (M2e5x virus-like particles (VLP)) as a cross-protective influenza vaccine candidate. Co-delivery of influenza split vaccine and M2e5x VLP to the skin by MN patch was found to confer effective protection against heterosubtypic influenza virus by preventing weight loss and reducing lung viral loads. Compared to intramuscular immunization, MN-based delivery of combined split vaccine and M2e5x VLPs shaped cellular immune responses toward T helper type 1 responses increasing IgG2a isotype antibodies as well as IFN-γ producing cells in mucosal and systemic sites. This study provides evidence that potential immunological and logistic benefits of M2e5x VLP with human influenza split vaccine delivered by MN patch can be used to develop an easy-to-administer cross-protective influenza vaccine.
Highlights
Current influenza vaccines do not provide good protection against antigenically distinct strains due to strain-specific protection on the basis of hemagglutinin (HA) subtypes
The present study investigates humoral and cellular immunogenicity as well as heterosubtypic protection of an influenza split vaccine co-immunized with M2e5x virus-like particles (VLPs) through skin immunization using MN delivery
Human influenza split vaccine derived from the 2009 pandemic strain of A/California/07/2009 (H1N1) virus was generously provided by Green Cross (Yongin-si, Korea) or Seqirus (Maidenhead, United Kingdom)
Summary
Current influenza vaccines do not provide good protection against antigenically distinct strains due to strain-specific protection on the basis of hemagglutinin (HA) subtypes. To overcome narrow strain-specific protection and to effectively control a pandemic outbreak, new strategies of conferring broadly cross-protective immunity against antigenically different influenza strains are under development [6,7]. Recent approaches were demonstrated to induce heterosubtypic cross protection by influenza vaccination using MNs non-neutralizing M2e immunity alone would not be sufficient for conferring sufficient protection against circulating and antigenically different strains [16,17]. In an effort toward achieving more effective vaccine delivery of a broadly protective vaccine that provides protection against circulating and antigenically different multiple strains of influenza, we hypothesized that the MN-based co-delivery of licensed influenza split vaccine and M2e5x VLPs as a conserved molecular antigen would overcome strain-specific protection of a current vaccination strategy. The present study investigates humoral and cellular immunogenicity as well as heterosubtypic protection of an influenza split vaccine co-immunized with M2e5x VLPs through skin immunization using MN delivery
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