Microneedle vaccination with stabilized recombinant XXXX virus hemagglutinin induces improved protective immunity.

@entity19 @entity1707 @entity30442 @entity683
The emergence of the @entity1707 -origin 2009 @entity683 pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated @entity683 virus or virus-like particles as skin-based vaccines. However, most currently available @entity683 vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit @entity683 vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that @entity19 vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 ( @entity30442 had significantly higher immune responses than did @entity19 vaccinated with unmodified sHA. These @entity19 were fully protected against a lethal challenge with @entity683 virus. Analysis of postchallenge lung titers showed that MN-immunized @entity19 had completely cleared the virus from their lungs, in contrast to @entity19 given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated @entity19 and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit @entity683 vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.
