Improved protection against avian influenza H5N1 virus by a single vaccination with virus-like particles in skin using microneedles

Abstract

Summary To develop a more effective vaccination method against H5N1 virus, we investigated the immunogenicity and protective efficacy after skin vaccination using microneedles coated with influenza virus-like particles containing hemagglutinin derived from A/Vietnam/1203/04 H5N1 virus (H5 VLPs). A single microneedle vaccination of mice with H5 VLPs induced increased levels of antibodies and provided complete protection against lethal challenge without apparent disease symptoms. In contrast, intramuscular injection with the same vaccine dose showed low levels of antibodies and provided only partial protection accompanied by severe body weight loss. Post-challenge analysis suggested that improved protection was associated with lower lung viral titers and enhanced generation of recall antibody secreting cells by microneedle vaccination. Thus, this study provides evidence that skin delivery of H5 VLP vaccines using microneedles designed for self-administration induces improved protection compared to conventional intramuscular immunization.

Long-Term Protective Immunity from an Influenza Virus-Like Particle Vaccine Administered with a Microneedle Patch

“…Different types of microneedle influenza vaccines and efficacies have been demonstrated. Substantial amounts of viral loads with a range of 10 4 -to 10 5 -PFU titers were detected in mice that were immunized on the skin using microneedles coated with 0.4 to 2 g H5 HA VLPs derived from influenza A/Vietnam/1203/04 virus (21,35). Also, 10 2 -to 10 3 -PFU lung viral titers and weight losses of 5 to 10% were observed in mice immunized with microneedle vaccines coated with 3 g of split A/Brisbane/59/2007 vaccine, which are approximately 10-to 50-fold less than the infected naive control group (36).…”

“…Thus, vaccine delivery via skin has been suggested to be an attractive approach for vaccination, especially using a microneedle patch (16)(17)(18)(19)(20)(21)(22)(23). Microneedles are micrometer-scale needles that can be coated with vaccine for simple, painless, and targeted delivery of the vaccine to the skin (24).…”

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

“…Using similar strategies, Song et al proved that H5N1 avian influenza VLP-constituted MAs induced long-lasting B-and T-cell responses with improved protection in mice. 74,75 Also, Pearton et al found that influenza VLP-based MAs could initiate a stimulatory response in Langerhans cells (LCs) through deposition of the vaccine in human skin. 12 And further exploration of the complex molecular and cellular host responses to influenza VLP MAs revealed up-regulation of a host of genes responsible for key immunomodulatory processes and host viral response following microneedle injection of VLPs.…”

Protective Effect of Korean Red Ginseng Extract on the Infections by H1N1 and H3N2 Influenza Viruses in Mice

“…As a measure of influenza virus growth, culture supernatants on MDCK cells were used to determine hemagglutination activity titers as described. 33 An equal volume of 1% chicken red blood cells and culture supernatants from infected MDCK cells was incubated at room temperature for 1 h. The hemagglutination activity titers were expressed as the reciprocal of the highest dilution of culture supernatants preventing the formation of visible erythrocyte aggregates.…”