Vassilieva Elena V, Kalluri Haripriya, McAllister Devin, Taherbhai Misha T, Esser E Stein, Pewin Winston P, Pulit-Penaloza Joanna A, Prausnitz Mark R, Compans Richard W, Skountzou Ioanna
Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.
Drug Deliv Transl Res. 2015 Aug;5(4):360-71. doi: 10.1007/s13346-015-0228-0.
Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study, we evaluated the immunogenicity of H1N1, H3N2, and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25 °C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by single radial diffusion (SRID) assay and immune responses to vaccination in BALB/c mice. After a single immunization, all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least 3 months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability.
预防季节性流感流行和大流行依赖于广泛的疫苗接种覆盖率以诱导保护性免疫。除了与流行病毒有良好的抗原匹配外，三价疫苗中各毒株的有效性还取决于其免疫原性。在本研究中，我们评估了通过新型溶解微针贴片单独递送的H1N1、H3N2和B型季节性流感病毒疫苗毒株的免疫原性，以及该制剂在25°C储存期间的稳定性。我们的数据表明，通过单向辐射扩散（SRID）测定法以及对BALB/c小鼠进行疫苗接种后的免疫反应测量，所有毒株在掺入溶解贴片后均保留了其抗原活性。单次免疫后，与肌肉注射相比，通过微针贴片递送的所有三种抗原均诱导出更高的中和抗体滴度。皮肤抗原递送对免疫原性较低的B毒株尤其有益。用包裹甲型/布里斯班/59/07（H1N1）流感疫苗的溶解微针贴片免疫的小鼠对同源小鼠适应的流感病毒致死性攻击具有完全保护作用。通过SRID测定法体外测量以及通过小鼠免疫研究体内测量，所有疫苗成分在室温下储存至少3个月期间均保持活性。我们的数据表明，由于使用免疫原性较低的流感抗原可改善免疫反应并增强稳定性，溶解微针贴片是流感皮肤疫苗接种的一项有前景的进展。
