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  • 1
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    Programming the magnitude and persistence of antibody responses with innate immunity (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-02-26
    Description: Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for 〉1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057367/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasturi, Sudhir Pai -- Skountzou, Ioanna -- Albrecht, Randy A -- Koutsonanos, Dimitrios -- Hua, Tang -- Nakaya, Helder I -- Ravindran, Rajesh -- Stewart, Shelley -- Alam, Munir -- Kwissa, Marcin -- Villinger, Francois -- Murthy, Niren -- Steel, John -- Jacob, Joshy -- Hogan, Robert J -- Garcia-Sastre, Adolfo -- Compans, Richard -- Pulendran, Bali -- HHSN266200700006C/PHS HHS/ -- HHSN266200700010C/PHS HHS/ -- N01 AI50025/AI/NIAID NIH HHS/ -- R01 AI048638/AI/NIAID NIH HHS/ -- R01 AI048638-07/AI/NIAID NIH HHS/ -- R01 AI048638-08/AI/NIAID NIH HHS/ -- R01 DK057665/DK/NIDDK NIH HHS/ -- R01 DK057665-09/DK/NIDDK NIH HHS/ -- R01 DK057665-10/DK/NIDDK NIH HHS/ -- R01 DK057665-11/DK/NIDDK NIH HHS/ -- R01 DK057665-12/DK/NIDDK NIH HHS/ -- R01 DK057665-13/DK/NIDDK NIH HHS/ -- R01DK057665/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 AI048638-09A1/AI/NIAID NIH HHS/ -- R37 AI048638-10/AI/NIAID NIH HHS/ -- R37 AI048638-11/AI/NIAID NIH HHS/ -- R37AI48638/AI/NIAID NIH HHS/ -- R56 AI048638/AI/NIAID NIH HHS/ -- R56 AI048638-09/AI/NIAID NIH HHS/ -- U01AI070469/AI/NIAID NIH HHS/ -- U19AI057266/AI/NIAID NIH HHS/ -- U19AI090023/AI/NIAID NIH HHS/ -- U54AI057157/AI/NIAID NIH HHS/ -- U54AI57158/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Feb 24;470(7335):543-7. doi: 10.1038/nature09737.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, Emory University, Atlanta, Georgia 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21350488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/biosynthesis/*immunology ; Antibodies, Viral/biosynthesis/*immunology ; Antibody Formation/*immunology ; Dendritic Cells/cytology/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Immunity, Innate/*immunology ; Immunologic Memory/*immunology ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H5N1 Subtype/immunology ; Influenza Vaccines/administration & dosage/*immunology ; Lactic Acid ; Ligands ; Lymph Nodes/cytology/immunology ; Lymphocyte Activation ; Macaca mulatta/immunology/virology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nanoparticles/administration & dosage ; Plasma Cells/cytology/immunology/metabolism ; Polyglycolic Acid ; T-Lymphocytes/immunology ; Toll-Like Receptors/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    CXCL13 is a biomarker of germinal center activity [Immunology and Inflammation] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-03-09
    Description: Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) ligand 13] were associated with the generation of broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort of HIV-infected individuals. Germinal centers (GCs) perform the remarkable task of optimizing B-cell Ab responses. GCs are required for almost all B-cell...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Influence of solar wind–magnetosphere coupling functions on the Dst index (2011)
    Wiley
    Details
    Publication Date: 2011-12-30
    Description: In this paper we investigate the role of different solar wind magnetosphere coupling functions on the Dst index calculated by the low-order nonlinear dynamical WINDMI model. In our previous work we have shown that the geotail current dynamics has a significant role in the two-phase decay of the Dst index. During that investigation we used the rectified solar wind electric field vxBz as a baseline for the simulations and analysis. Here we include an evaluation of four other coupling functions in addition to the rectified vBs. These coupling functions emphasize different physical mechanisms to explain the energy transfer into the magnetosphere due to solar wind velocity, dynamic pressure, magnetic field, and Mach number. One coupling function is due to Siscoe, another by Borovsky, and two by Newell. Our results indicate that for a majority of cases, at most only vx, By, and Bz are needed to sufficiently account for the supply of energy to the ring current and geotail current components that contribute to the Dst index. The more complex coupling functions sometimes perform extremely well on storm data sets but at other times do not reproduce the Dst index faithfully. The AL index was used as an additional constraint on the allowable geotail current dynamics and to further differentiate between coupling functions when the Dst performance was similar. The solar wind dynamic pressure contribution appears to be correctly accounted for through the calculation of the Dmp formula of Burton et al. (1975). The degree to which the By component affects the Dst index is not entirely clear from our results, but in most cases its inclusion slightly overemphasizes the ring current contribution and slightly underemphasizes the geotail current contribution.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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