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6. Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice

Author

Zhu, Qing, Egelston, Colt, Gagnon, Susan, Sui, Yongjun, Belyakov, Igor M., Klinman, Dennis M., and Berzofsky, Jay A.

Subjects
T cells -- Properties, Ligands (Biochemistry) -- Properties, Immune response -- Observations, Adjuvants, Pharmaceutic -- Dosage and administration, Health care industry
Abstract

TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Rα, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses., Introduction There has been an increasing global threat by the recent emergence of many viral infectious diseases, including HIV/AIDS, avian influenza, SARS, Ebola, and West Nile virus. Vaccination promises to [...]

Published
2010
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12. TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4+ memory T cell loss in SIVmac251-challenged rhesus macaques

Author

Sui, Yongjun, primary, Gagnon, Susan, additional, Dzutsev, Amiran, additional, Zhu, Qing, additional, Yu, Huifeng, additional, Hogg, Alison, additional, Wang, Yichuan, additional, Xia, Zheng, additional, Belyakov, Igor M., additional, Venzon, David, additional, Klinman, Dennis, additional, Strober, Warren, additional, Kelsall, Brian, additional, Franchini, Genoveffa, additional, and Berzofsky, Jay A., additional

Published
2011
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21. TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4+ memory T cell loss in SIVmac251-challenged rhesus macaques

Author

Sui, Yongjun, Gagnon, Susan, Dzutsev, Amiran, Zhu, Qing, Yu, Huifeng, Hogg, Alison, Wang, Yichuan, Xia, Zheng, Belyakov, Igor M., Venzon, David, Klinman, Dennis, Strober, Warren, Kelsall, Brian, Franchini, Genoveffa, and Berzofsky, Jay A.

Subjects
*IMMUNOLOGICAL adjuvants, *RHESUS monkeys, *VIRAL load, *GENE expression, *EPITOPES, *CHEMOKINES, *T cells, *DRUG development, *HIV
Abstract

Abstract: Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4+ T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4+ T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8+ tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer+ T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4+ T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer+ T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4+ T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4+ T cell levels and SIV viral load. [ABSTRACT FROM AUTHOR]

Published
2011
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22. Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques.

Author

Yongjun Sui, Qing Zhu, Gagnon, Susan, Dzutsev, Amiran, Terabe, Masaki, Vaccari, Monica, Venzon, David, Klinman, Dennis, Strober, Warren, KeIsaII, Brian, Franchini, Genoveffa, Belyakov, Igor M., and Berzofsky, Jay A.

Subjects
SIMIAN viruses, IMMUNITY, MACAQUES, IMMUNOLOGICAL adjuvants, T cell receptors, MUCOUS membranes, POXVIRUSES, DISEASES
Abstract

Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques. and made three critical observations regarding both innate and adaptive correlates of protection: (I) adjuvant-alone without vaccine antigen impacted the intrarectal SlVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8+ T cells correlated with protection, not tetramer+ T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Rα, which can present IL-15 in trans. as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity. [ABSTRACT FROM AUTHOR]

Published
2010
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23. Conversion of a T Cell Antagonist into an Agonist by Repairing a Defect in the TCR/Peptide/MHC Interface Implications for TCR Signaling

Author

Baker, Brian M., Gagnon, Susan J., Biddison, William E., and Wiley, Don C.

Abstract

The structure of the A6 αβTCR/HTLV-1 Tax-peptide/MHC I complex with proline 6 of Tax substituted with alanine (P6A), an antagonist, is nearly identical to the structure with wild-type Tax agonist. Neither the proline in the agonist nor the alanine in the antagonist is contacted by the αβTCR. Here, we demonstrate that antagonist activity of P6A is associated with low affinity of the A6 αβTCR for Tax-P6A/HLA-A2. We show that stepwise repair of a packing defect in the TCR/MHC interface using N-alkylated amino acids results in stepwise increases in TCR affinity and activity. Kinetic and thermodynamic measurements suggest that for some ligands the range of T cell outcomes does not correlate with either their αβTCR affinity or the half-life of the αβTCR/peptide/MHC complex.

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24. Bystander Target Cell Lysis and Cytokine Production by Dengue Virus-Specific Human CD4+Cytotoxic T-Lymphocyte Clones

Author

Gagnon, Susan J., Ennis, Francis A., and Rothman, Alan L.

Abstract

ABSTRACTDengue hemorrhagic fever, the severe form of dengue virus infection, is believed to be an immunopathological response to a secondary infection with a heterologous serotype of dengue virus. Dengue virus capsid protein-specific CD4+cytotoxic T-lymphocyte (CTL) clones were shown to be capable of mediating bystander lysis of non-antigen-presenting target cells. After activation by anti-CD3 or in the presence of unlabeled antigen-presenting target cells, these clones could lyse both Jurkat cells and HepG2 cells as bystander targets. Lysis of HepG2 cells suggests a potential role for CD4+CTL in the liver involvement observed during dengue virus infection. Three CD4+CTL clones were demonstrated to lyse cognate, antigen-presenting target cells by a mechanism that primarily involves perforin, while bystander lysis occurred through Fas/Fas ligand interactions. In contrast, one clone used a Fas/Fas ligand mechanism to lyse both cognate and bystander targets. Cytokine production by the CTL clones was also examined. In response to stimulation with D2 antigen, CD4+T-cell clones produced gamma interferon, tumor necrosis factor alpha (TNF-a) and TNF-ß. The data suggest that CD4+CTL clones may contribute to the immunopathology observed upon secondary dengue virus infections through direct cytolysis and/or cytokine production.

Published
1999
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25. Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count >= 300 cells/mu L who were assigned to 7.5 MIU interleukin-2

Author

Fox, Zoe, Antunes, Francisco, Davey, Rick, Gazzard, Brian, Klimas, Nancy, Labriola, Ann, Losso, Marcelo, Neaton, James D., Phillips, Andrew N., Ruxrungtham, Kiat, Staszewski, Schlomo, Weiss, Laurence, Lundgren, Jens D., Abrams, Donald I., Cooper, David A., Darbyshire, Janet H., Duncan, William R., Emery, Sean, Lane, H. Clifford, Lehrman, Sandra, Aguilar, Liliana, Betina Angel, Eleonora, Aquilia, Silvia, Belloso, Waldo, Benetucci, Jorge, Bittar, Victor, Cahn, Pedro, Casiro, Arnaldo, Contarelli, Jorge, Corral, Jorge, Daciuk, Lucia, David, Daniel, Ferrari, Ines, Fridman, Diego, Galache, Viviana, Guaragna, Graciela, Ivalo, Silvina, Laplume, Hector, Lanusse, Isabel, Lasala, Maria B., Lattes, Roberta, Lasovsky, Jaime, Lopardo, Gustavo, Lourtau, Leonardo, Lupo, Sergio, Maranzana, Aldo, Marson, Cristina, Massera, Lucila, Del Lujan Sanchez, Marisa, Somenzini, Carla, Tocci, Mariel, Algar, Sally, Anderson, Jonathan, Baker, David, Blavius, Kathy, Bloch, Mark, Boyle, Michael, Bradford, David, Britton, Phillip, Carrall, Leah, Carr, Andrew, Chuah, John, Curry, Michael, D Arcy-Evans, Clive, Dobson, Pauline, Doong, Nicholas, Egan, Cari, Ferguson, Wendy, Finlayson, Robert, French, Martyn, Frater, Anthony, Gold, Julian, Habel, Philip, Haig, Kay, Holland, Rohan, Hyland, Natalie, Hoy, Jennifer, Hudson, Jeff, James, Robyn, Leung, Jenny, Lowe, Kaye, Macrae, Karen, Mcmurchie, Marilyn, Medland, Nicholas, Miller, Samantha, Murray, Jo, Newman, Rosie, Orth, David, Patching, Julie, Primrose, Ruth, Ree, Hugo, Richardson, Robyn, Rogers, Gary, Roney, Janine, Roth, Norman, Sarangapany, Jeganathan, Shaw, David, Silberberg, Carol, Skett, Jenny, Williams, Leah, Soo, Tuck Meng, Sowden, David, Street, Alan, Vale, Robyn, Villella, Claudio, Walker, Alan, Watson, Ashley, Wendt, Ngaire, Wood, Helen, Youds, David, Aichelburg, Alexander, Rieger, Armin, Vetter, Norbert, Clumeck, Nathan, Wit, Stephane, Kabeya, Kabamba, O Doherty, Elizabeth, Amorim, Cristiane Sales, Basso, Caritas Relva, Lewi, David Salamao, Pereira, Luiz Carlos, Da Silva, Mariliza, Lobato Souza, Tamara Newman, Angel, Jonathan, Bouchard, Pierrette-Rolande, Clark, Fran, Cohen, Jeff, Dambreville, Mimose, Ellis, Michele, Fiset, Stephan, Foster, Andrea, Fraser, Christopher, Gagnon, Susan, Gilmour, Janet, Guenette, Richard, Haldane, Heather, Hawley-Foss, Nanci, Hyndman, Susan, Johnston, Lynn, Jubinville, Nathalie, Juneau, Francoise, Kelleher, Lynn, Lapointe, Lyne, Latendre-Paquette, Judy, Lindemulder, Adeline, Mashinter, Laura, Lefebvre, Eric, Mcfarland, Nancy, Morisseau, Chantal, O Neill, Robert, Piche, Alain, Ralph, Edward, Rouleau, Danielle, Routy, Jean-Pierre, Sandre, Roger, Schmidt, Shelley, Shafran, Stephen, Smaill, Fiona, Stromberg, Dale, Trepanier, Jean-Marc, Trottier, Sylvie, Veal, Susanne, Walmsley, Sharon, Weiss, Karl, Williams, Kurt, Young, Mavis, Zaleschuk, Barbara, Zarowny, Don, Baadegaard, Bente, Black, Finn, Boedker, Kirsten, Gerstoft, Jan, Jensen, Lene, Mathiesen, Lars, Nielsen, Henrik, Pedersen, Court, Petersen, Dorthe, Aboulker, Jean-Pierre, Baakili, Adyb, Bengrait, Nafissa, Bensalem, Maryse, Berthe, Huguette, Bloche, Martin, Bazin, Claude, Boue, Francois, Bouvet, Elisabeth, Brancon, Christiane, Capitant, Catherine, Ceppi, Carole, Cheneau, Christine, Coutellier, Anne, Chennebault, Jean Marie, Coquet, Fabienne, Truchis, Pierre, Delavalle, Anne-Marie, Frixon-Marin, Veronique, Gastaut, Jean-Albert, Delfraissy, Francois, Eliaszeicz, Muriel, Gallais, Herve, Gataut, Jean-Albert, Gilquin, Jacques, Gonzalez-Canali, Gustavo, Gaudebout, Chrisiane, Goujard, Cecile, Hoen, Bruno, Honore, Patricia, Jarousse, Bernard, Lang, Jean-Marie, Lefebvre, Benedict, Levy, Yves, Loison, Jocelyne, Maignan, Aline, Meynard, Jean-Luc, Michon, Christophe, Mole, Martin, Marsal, Laurence, Matheron, Sophie, Mortier, Emmanuel, Oksenhendler, Eric, Poirier, Sandrine, Picard-Dahan, Catherine, Ravaux, Isabelle, Raffi, Francois, Raguin, Gilles, Reynes, Jacque, Rozenbaum, Willy, Salmon, Dominique, Simon, Anne, Spiridon, Gabriella, Viard, Jean-Paul, Vidal, Michele, Zucman, David, Bergmann, Frank, Brockmeyer, Norbert, Faetkenheuer, Gerd, Fenske, Stefan, Gey, Daniela, Goebel, Frank-Detlef, Goetsch, Martina, Hartmann, Martin, Klinker, Hartwig, Kremer, Gisela, Mantzsch, Kathleen, Mauss, Stefan, Rockstroh, Juergen, Rotty, Jessica, Rund, Ellen, Schneider, Katrin, Schuermann, Dirk, Staszweski, Schlomo, Tilmann, Klaus, Vogel, Martin, Bentwich, Zvi, Drora, Goldstain, Kedem, Eynat, Lang, Ruth, Levi, Itzic, Maayan, Shlomo, Magen, Eli, Mamorsky, Merav, Pilpul, Anat, Pollack, Shimon, Sthoeger, Zev, Vered, Hadas, Yust, Israel, Lyons, Fiona, Mulcahy, Fiona, Rochford, Annette, Auiti, Fernando, Angarano, Gioacchino, Bertelli, Davide, Bini, Teresa, Bruno, Raffaele, Cadeo, Gian Pietro, Carosi, Giampietro, D Arminio Monforte, Antonella, Del Giacco, Sergio, Di Pietro, Massimo, Esposito, Roberto, Filice, Gaetano, Gavazzeni, Gabriella, Guaraldi, Giovanni, Indiveri, Francesco, Lazzarin, Adriano, Mazzotta, Francesco, Minolli, Lorenzo, Montroni, Maria, Moroni, Mauro, Nozza, Silvia, Pastor, Guiseppe, Poli, Guido, Raise, Enzo, Romagnani, Sergio, Rusconi, Vega, Sacchi, Paolo, Suter, Fredy, Tambussi, Giuseppe, Tirelli, Umberto, Fraser, Helen, Iwamoto, Aikichi, Kikuchi, Yoshida, Mori, Masahiko, Nakamura, Tetsuya, Odawara, Takashi, Oka, Shinichi, Shirasaka, Takuma, Takano, Misao, To, Junichiro, Ueta, Chisato, El Filali, Kamal, Erradey, Ikbale, Himmich, Hakima, Blok, W., Borleffs, J., Bravenboer, B., Bronveld, W., Claessen, F., Duurvoort, Maurice, Ferwerda, J., Frissen, P., Hulshoff, Nicolette, Juttman, Job, Kauffmann, R., Koopmans, P., Kroon, F., Lowe, Selwyn, Leemhuis, M., Meenhorst, P., Boer, Lieselotte Posthuma, Reiss, Peter, Reinders-Folmer, S., Richter, C., Santegoets, Rick, Schoemaker, Marijke, Schrey, G., Sprenger, Herman, Ten Veen, Jacob, Tessalaar, Judith, Ende, M., Vall, H., Eeden, Arne, Leeuwen, Remko, Vermeulen, Joost, Ten Kate, Reinier W., Boxtel, Renee, Eden, Arne, Ven, Bernadette, Meulen, Piet, Ten Napei, C., Vriesendrop, R., Bruun, Johann, Bakowska, Elzbieta, Beniowski, Marek, Boron-Kaczmarska, Anna, Gasiorowski, Jacek, Gxadysz, Andrzej, Horban, Andrzej, Knysz, Brygida, Mularska, Elzbieta, Pynka, Magdelena, Szymczak, Aleksandra, Aldir, Isabel, Doroana, Manuela, Duque, Luis, Mansinho, Kamal, Pinto, Inez, Valadas, Emilia, Vera, Jose, Foo, Estelle, Panchalingham, Anushia, Lim, Poh Lian, Paton, Nick, Peperstraete, Bernard, Quek, Angela, Alcazar-Caballero, Rosario, Arrizabalaga, Julio, Bouza, Emilio, Cepeda, Concepcion, Barron, Xabier, Cervero Jimenez, Miguel, Clotet, Bonaventura, Cortes, Luis, Domingo, Pere, Fernandez, Pompeyo, Fernandez-Cruz, Eduardo, Fuster, Montserrat, Gatell, Jose, Gijon, Paloma, Gil, Ignacio, Gonzales-Lahoz, Juan, Gonzalez, Alicia, Hernandez, Manuel, Iribarren, Jose, Jimenez, Miguel, Knobel, Hernando, Leon, Agathe, Carlos Lopez, Juan, Lozano, Angeles, Lopez, Paco, Moreno, Jose, Munoz, Rosa, Padilla, Belen, Parras, Angeles, Pastor, Antoni, Pedreira, Jose, Pristo, Julio, Pena, Jose, Roca, Victor, Rubio, Rafael, Sanchez Rivera, Jose, Sanz, Jesus, Tamargo, Lara, Torres, Rafael, Pehrson, Pehr O., Sandstrom, Eric, Bernasconi, Enos, Gurtner, Vanina, Magenta, Lorenzo, Ampunpong, Uangarun, Bowonwatnuwong, Chureeratana, Chanchai, Patimoaporn, Chetchotisakd, Ploenchan, Chuenyam, Thesinee, Duncombe, Chris, Horsakulthai, Mannassinee, Kantipong, Pacharee, Liddy, John, Phanuphak, Praphan, Pongsurachet, Vithaya, Seekaew, Samroeng, Sonjai, Areerat, Subsri, Nuramon, Suwanagool, Surapol, Techasathit, Wichai, Wankoon, Jaturaporn, Adebiyi, Aderonke, Aldam, Diana, Alexander, Ian, Angus, Brian, Barber, Tristan, Bonnington, Sue, Care, Chris, Carroll, Anne, Cornforth, David, Donaldson, Oscar, Druiff, Laurance, Easterbrook, Philippa, Edwards, Beverley, Ellis, Chris, Fisher, Martin, Fox, Ray, Harrison, Allan, Herman, Sandra, Heald, Lisa, Higgs, Christopher, Jendrulek, Isabelle, Johnson, Margaret, Judges, Lucy, Karim, Fatimah, Kinghorn, George, Laurenti, Julie, Lee, Christine, Leen, Clifford, Legg, Ken, Maw, Raymond, Macconachie, Alisdair, Mckernan, Sinead, Mclean, Lorna, Mcmillan, Andrew, Mguni, Sifiso, Morris, Sheila, Mulchay, Fiona, Mullan, Dee, Mullaney, Scott, Murphy, Maurice, Nunn, Andrew, Ong, Edmund, Owen, Maxine, Palfreeman, Adrian, Perry, Nicky, Peters, Barry, Pozniak, Anton, Ronan, Agnes, Skinner, Cecilia, Stroud, Carol, Takawira, Martin, Tamm, Norbert, Thomas, Rachel, Yee, Thynn Thynn, Vanthuyne, An, Wansborough-Jones, Mark, Weber, Jonathan, White, David, Wilkins, Ed, Wiselka, Martin, Williams, Ian, Waugh, Mike, Wotherspoon, Joyce, Youle, Mike, Doyle, Margaret, Goodwin, Edward, Luskin-Hawk, Roberta, Sullivan, James, Verheggen, Rita, Abrams, Donald, Baxter, John, Besch, C. Lynn, Child, Carroll, Cohn, David, Cooper, Pam, El-Sadr, Wafaa, Farrough, Martha, Fisher, Evelyn, Fuentes, Luis, Gordin, Fred, Graeber, Carol, Kelly, Mary Ellen, Kostman, Jay, Lattanzi, Kelly, Macarthur, Rodger, Makohon, Linda, Markowitz, Norman P., Martinez, Norma, Mastro-Polak, Diane, Mitchell, Vinnie, Mushatt, David, Patterson, Kathryn, Perez, George, Rosmarin, Corey, Rouff, Jack R., Saldanha, Jennifer, Sampson, James, Sawyer, Robert, Standridge, Barbara, Sweeton, Bentley, Tedaldi, Ellen, Thompson, Melanie, Valencia, Patricia, Verlinghieri, Gwen, Walker, Janice, Watson, Vicky, Williams, Bruce, Armstrong, Adam, Banks, Susan, Blazes, David, Barile, Anthony, Coelho, Linda, Dennis, Marilyn, Flaks, Hannah, Gilcrest, Joyce, Gittens, Kathleen, Hopper, Shelia, Humphries, M. J., Spooner, Katherine, Tamminga, Cindy L., Vita, Jean, Wegner, Scott A., Wortmann, Glenn, Bisby, Nicole, Blake, William, Brown, Sheldon, Chilliade, Phillippe, Cole, Teresa, Elliot, Katherine, Geisler, Christiane, Goetz, Matthew, Gomez-Perez, Elizabeth, Helman, Jami, Nahass, Ronald, Leflore, Dirk, Marston, Barbara, Obregon, Maria, Petrolati, Jennifer, Pitrak, David L., Roland, Robert, Rosa, Carol, Rossman, Barbara, Schlueter Wirtz, Susan, Schuck, Suzanne, Scretchings, Tiffany, Simon, Gary, Smith, Mack, Summers, Kimberley, Werhane, Mary Jo, Arduino, Roberto, Bell, Brian, Breaux, Katherine, Cuervo, Hilda, Hale, Carl, Lewis, Stanley, Mall, Mark, Mora, Fransisco, Diez, Martine M., Okhuysen, Pablo, Rodriguez-Barradas, Maria, Schrader, Shannon R., Healy, Lynn, Kaszubski, Chris, Kolber, Michael, Tanner, Tom, Armstrong, Joann, Dahlke, Jennifer, Johnson, Leonard, Kaminski, Patricia, Rhame, Frank, Shoden, Cheryl, Temesgen, Zelalem, Urbanich, Marcy, Valenti, Sharon, Zervos, Marcus, Barrick, Bill, Chaitt, Doreen, Hahn, Barbara, Lane, Cliff, Martell, Dennis, Mcnay, Laura, Metcalf, Julia, Powers, April, Tavel, Jorge A., Loveless, Karen, Peterson, Sue, Sweek, Suzanne, Albrecht, Helmut, Antoine, Nicole, Pell, Paula, Gatell, Jose Maria, Hoy, Jenny, Lifson, Alan, Pederson, Court, Borup, Liselotte, Dragsted, Ulrik Bak, Greve, Anne Fau, Jensen, Karoline, Jens Lundgren, Mollerup, David, Pearson, Mary, Phillips, Andrew, Aboulhab, Jamila, Babiker, Abdel, Cordwell, Brooke, Darbyshire, Janet, Hack, Lisa, Hooker, Malcolm, Moraes, Yolanda, Newberry, Douglas, Nuwagaba-Biribonwoha, Harriet, Hooff, Fionna, Denning, Eileen, Holland Klemme, Leslie, Carey, Cate, Chan, Fonnie, Cooper, David, Courtney-Rodgers, David, Drummond, Fraser, Jacoby, Simone, Law, Matthew, Stewart, Morgan, Pett, Sarah, Alloo, Zarina, Bebchuk, Judy, Bollenbeck, Patty, Duchene, Alain G., Fosdick, Lisa, Harrison, Merrie, Krum, Eric, Larson, Gregg, Meger, Sue, Neaton, James, Nelson, Ray, Quan, Siu-Fun L., Schultz, Terri, Telke, Susan, Thackeray, Lisa, Thompson, Greg, Wentworth, Deborah, Wyman, Nicole, Duncan, William, Ferguson, Elaine, Fox, Lawrence, Gettinger, Nikki, Herrera, Janet, Luzar, Mary Anne, Maeshiro, Mieko, Martinez, Ana, Oseekey, Karen, Baigent, Greg, Capra, William, Duliege, Anne-Marie, Fitzgerald, Linda, Kwakkelstein, Marthin, Maral, Jean, O Hara, Mary, Sahner, David, Weber, Claire, Adam-Perchec, Christine, Barron, Nigel, Bell, Mary Louise, Dolan, Sandra, Eckstrand, Julie, Hicks, Steven, Mcauley, George, Beck, Sharon, Brown, Shawn, and Rupert, Adam

26. More Chamber Music at the Conference!

Author

Gagnon, Susan

Abstract

The article focuses on the Chamber Music teams that participated in the 2010 Suzuki Association of the Americas Inc. Conference. Aside from the preformed groups that participated in the master classes, the event also featured non-preformed chamber groups. She reveals that the preformed groups were given the opportunity to perform at the Orchestra Hall before the Minnesota Orchestra concerts. She adds that the groups impressed the audience with their professionalism and diversity.

Published
2010

27. Mail Bag.

Author

Cassella, Sheryl, Savage, Susan, Hutcheson-Cobbs, Rita, Moss, Heather, Desharnais, Aimee, Pacheco, Melissa M., and Gagnon, Susan

Subjects
LETTERS to the editor, WEIGHT loss, TENNIS players
Abstract

Several letters to the editor are presented in response to the article “Half Their Size," as well as articles on the tennis player Venus Williams and Lisa Niemi Swayze, wife of the late actor Patrick Swayze.

Published
2012

28. Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice.

Author

Qing Zhu, Egelston, Colt, Gagnon, Susan, Yongjun Sui, Belyakov, Igor M., Klinman, Dennis M., Berzofsky, Jay A., Zhu, Qing, and Sui, Yongjun

Subjects
*LIGANDS (Biochemistry), *LABORATORY mice, *T cells, *ANTIVIRAL agents, *COMMUNICABLE diseases
Abstract

TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Ralpha, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses. [ABSTRACT FROM AUTHOR]

Published
2010
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