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Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties
Kim, Mi Young,Copland, Alastair,Nayak, Kaustuv,Chandele, Anmol,Ahmed, Muhammad S.,Zhang, Qibo,Diogo, Gil R.,Paul, Matthew J.,Hofmann, Sven,Yang, Moon‐,Sik,Jang, Yong‐,Suk,Ma, Julian K BLACKWELL 2018 PLANT BIOTECHNOLOGY JOURNAL Vol.16 No.7
<P><B>Summary</B></P><P>Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant expression to produce a humanized and highly immunogenic poly‐immunoglobulin G scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor‐targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralizing antibodies and evidence of cell‐mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue <I>ex vivo</I> as evidenced by antigen‐specific CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T‐cell proliferation, IFN‐γ and antibody production. The purified polymeric fraction of dengue PIGS (D‐PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low‐affinity Fcγ receptors on antigen‐presenting cells. These results show that the plant‐expressed D‐PIGS have the potential for translation towards a safe and easily scalable single antigen‐based tetravalent dengue vaccine.</P>
Seong, Y.B.,Owen, L.A.,Caffee, M.W.,Kamp, U.,Bishop, M.P.,Bush, A.,Copland, L.,Shroder, J.F. Elsevier 2009 Geomorphology Vol.107 No.3
Basin-wide rockwall retreat rates are estimated using cosmogenic <SUP>10</SUP>Be concentrations in supraglacial debris from the Baltoro Glacier basin in K2 region of the Central Karakoram, Pakistan. Total cosmogenic <SUP>10</SUP>Be concentrations of the supraglacial debris were measured using accelerator mass spectrometry to determine <SUP>10</SUP>Be concentrations inherited from the rockwalls within the glaciated basin. Given that rockfall induced by periglacial weathering and snow and ice avalanches is the most important source of supraglacial debris production in the high mountain glaciated basin, the erosion rate of the bare bedrock can be considered to be the rate of rockwall retreat. The rate of the rockwall erosion, converted from the calculated inheritance of <SUP>10</SUP>Be concentrations, using the maximum velocity of the active glacier, places an upper limit ranging from 0.65 mm/year to 2.48 mm/year. This rate of rockwall retreat is in the same order of magnitude reported in other high Himalayan mountains. The rate, however, is an order of magnitude higher than erosion rates inferred from sediment budget studies and half that of the fluvial incision rate and exhumation rate for the same region. The difference between rates of basin-wide rockwall retreat and fluvial incision rates over the Late Quaternary suggests that in this glaciated basin fluvial incision is likely enhanced by localized/differential tectonism and/or isostatic uplift.