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        The osmotic stress response of split influenza vaccine particles in an acidic environment

        Hyo-Jick Choi,Min-Chul Kim,Sang-Moo Kang,Carlo D. Montemagno 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.12

        Oral influenza vaccine provides an efficientmeans of preventing seasonal and pandemic disease. In thiswork, the stability of envelope-type split influenza vaccineparticles in acidic environments has been investigated. Owing to the fact that hyper-osmotic stress can significantlyaffect lipid assembly of vaccine, osmotic stressinducedmorphological change of split vaccine particles, inconjunction with structural change of antigenic proteins,was investigated by the use of stopped-flow light scattering(SFLS), intrinsic fluorescence, transmission electronmicroscopy (TEM), and hemagglutination assay. Splitvaccine particles were found to exhibit a step-wise morphologicalchange in response to osmotic stress due todouble-layered wall structure. The presence of hyperosmoticstress in acidic medium (0.3 osmolarity, pH 2.0)induced a significant level of membrane perturbation asmeasured by SFLS and TEM, imposing more damage to antigenic proteins on vaccine envelope than can be causedby pH-induced conformational change at acidic iso-osmoticcondition. Further supports were provided by theintrinsic fluorescence and hemagglutinin activity measurements. Thus, hyper-osmotic stress becomes an importantfactor for determining stability of split vaccineparticles in acidic medium. These results are useful inbetter understanding the destabilizing mechanism of splitinfluenza vaccine particles in gastric environment and indesigning oral influenza vaccine formulations.

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

        Kim, M.C.,Lee, J.W.,Choi, H.J.,Lee, Y.N.,Hwang, H.S.,Lee, J.,Kim, C.,Lee, J.S.,Montemagno, C.,Prausnitz, M.R.,Kang, S.M. Elsevier Science Publishers 2015 Journal of controlled release Vol.210 No.-

        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.

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