7 results on '"Azzopardi, Kristy"'
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2. Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines—an exploratory sub-study of the BRACE trial
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Curtis, Nigel, Davidson, Andrew, Gardiner, Kaya, Gwee, Amanda, Jamieson, Tenaya, Messina, Nicole, Morawakage, Thilanka, Perlen, Susan, Perrett, Kirsten, Pittet, Laure, Sastry, Amber, Teo, Jia Wei, Orsini, Francesca, Lee, Katherine, Moore, Cecilia, Vidmar, Suzanna, Ali, Rashida, Dunn, Ross, Edler, Peta, Gell, Grace, Goodall, Casey, Hall, Richard, Krastev, Ann, La, Nathan, McDonald, Ellie, McPhate, Nick, Nguyen, Thao, Ren, Jack, Stevens, Luke, Alamrousi, Ahmed, Bonnici, Rhian, Dang, Thanh, Germano, Susie, Hua, Jenny, McElroy, Rebecca, Razmovska, Monica, Reddiex, Scott, Wang, Xiaofang, Anderson, Jeremy, Azzopardi, Kristy, Bennett-Wood, Vicki, Czajko, Anna, Mazarakis, Nadia, McCafferty, Conor, Oppedisano, Frances, Ortika, Belinda, Pell, Casey, Spry, Leena, Toh, Ryan, Velagapudi, Sunitha, Vlahos, Amanda, Wee-Hee, Ashleigh, Ramos, Pedro, De La Cruz, Karina, Gamage, Dinusha, Karunanayake, Anushka, Mezzetti, Isabella, Ong, Benjamin, Singh, Ronita, Sooriyarachchi, Enoshini, Nicholson, Suellen, Cain, Natalie, Brizuela, Rianne, Huang, Han, Abruzzo, Veronica, Bealing, Morgan, Bimboese, Patricia, Bowes, Kirsty, Burrell, Emma, Chan, Joyce, Cushnahan, Jac, Elborough, Hannah, Elkington, Olivia, Fahey, Kieran, Fernandez, Monique, Flynn, Catherine, Fowler, Sarah, Andrit, Marie Gentile, Gladanac, Bojana, Hammond, Catherine, Ma, Norine, Macalister, Sam, Milojevic, Emmah, Mojeed, Jesutofunmi, Nguyen, Jill, O’Donnell, Liz, Olivier, Nadia, Ooi, Isabelle, Reynolds, Stephanie, Shen, Lisa, Sherry, Barb, Spotswood, Judith, Wedderburn, Jamie, Younes, Angela, Legge, Donna, Bell, Jason, Cheah, Jo, Cobbledick, Annie, Lim, Kee, Elia, Sonja, Addlem, Lynne, Bourke, Anna, Brophy, Clare, Henare, Nadine, Jenkins, Narelle, Machingaifa, Francesca, Miller, Skye, Mitchell, Kirsten, Pitkin, Sigrid, Wall, Kate, Villanueva, Paola, Crawford, Nigel, Norton, Wendy, Tan, Niki, Chengodu, Thilakavathi, Dawson, Diane, Gordon, Victoria, Korman, Tony, O’Bryan, Jess, Agius, Sophie, Bannister, Samantha, Bucholc, Jess, Burns, Alison, Camesella, Beatriz, Carlin, John, Ciaverella, Marianna, Curtis, Maxwell, Firth, Stephanie, Guo, Christina, Hannan, Matthew, Hill, Erin, Joshi, Sri, Lieschke, Katherine, Mathers, Megan, Odoi, Sasha, Rak, Ashleigh, Richards, Chris, Steve, Leah, Stewart, Carolyn, Sudbury, Eva, Thomson, Helen, Watts, Emma, Williams, Fiona, Young, Angela, Glenn, Penny, Kaynes, Andrew, De Floy, Amandine Philippart, Buchanan, Sandy, Sondag, Thijs, Xie, Ivy, Edmund, Harriet, Byrne, Bridie, Keeble, Tom, Ngien, Belle, Noonan, Fran, Wearing-Smith, Michelle, Clarke, Alison, Davies, Pemma, Eastwood, Oliver, Ellinghaus, Alric, Ghieh, Rachid, Hilton, Zahra, Jennings, Emma, Kakkos, Athina, Liang, Iris, Nicol, Katie, O’Callaghan, Sally, Osman, Helen, Rajaram, Gowri, Ratcliffe, Sophia, Rayner, Victoria, Salmon, Ashleigh, Scheppokat, Angela, Stevens, Aimee, Street, Rebekah, Toogood, Nicholas, Wood, Nicholas, Bahaduri, Twinkle, Baulman, Therese, Byrne, Jennifer, Carter, Candace, Corbett, Mary, Dao, Aiken, Desylva, Maria, Dunn, Andrew, Gardiner, Evangeline, Joyce, Rosemary, Kandasamy, Rama, Munns, Craig, Pelayo, Lisa, Sharma, Ketaki, Sterling, Katrina, Uren, Caitlin, Colaco, Clinton, Douglas, Mark, Hamilton, Kate, Bartlett, Adam, McMullan, Brendan, Palasanthiran, Pamela, Williams, Phoebe, Beardsley, Justin, Bergant, Nikki, Lagunday, Renier, Overton, Kristen, Post, Jeffrey, Al-Hindawi, Yasmeen, Barney, Sarah, Byrne, Anthony, Mead, Lee, Plit, Marshall, Lynn, David, Benson, Saoirse, Blake, Stephen, Botten, Rochelle, Chern, Tee Yee, Eden, Georgina, Griffith, Liddy, James, Jane, Lynn, Miriam, Markow, Angela, Sacca, Domenic, Stevens, Natalie, Wesselingh, Steve, Doran, Catriona, Barry, Simone, Sawka, Alice, Evans, Sue, Goodchild, Louise, Heath, Christine, Krieg, Meredith, Marshall, Helen, McMillan, Mark, Walker, Mary, Richmond, Peter, Amenyogbe, Nelly, Anthony, Christina, Arnold, Annabelle, Arrowsmith, Beth, Ben-Othman, Rym, Clark, Sharon, Dunnill, Jemma, Eiffler, Nat, Ewe, Krist, Finucane, Carolyn, Flynn, Lorraine, Gibson, Camille, Hartnell, Lucy, Hollams, Elysia, Hutton, Heidi, Jarvis, Lance, Jones, Jane, Jones, Jan, Jones, Karen, Kent, Jennifer, Kollmann, Tobias, Lalich, Debbie, Lee, Wenna, Lim, Rachel, McAlister, Sonia, McDonald, Fiona, Meehan, Andrea, Minhaj, Asma, Montgomery, Lisa, O’Donnell, Melissa, Ong, Jaslyn, Ong, Joanne, Parkin, Kimberley, Perez, Glady, Power, Catherine, Rezazadeh, Shadie, Richmond, Holly, Rogers, Sally, Schultz, Nikki, Shave, Margaret, Skut, Patrycja, Stiglmayer, Lisa, Truelove, Alexandra, Wadia, Ushma, Wallace, Rachael, Waring, Justin, England, Michelle, Latkovic, Erin, Manning, Laurens, Herrmann, Susan, Lucas, Michaela, Lacerda, Marcus, Andrade, Paulo Henrique, Barbosa, Fabiane Bianca, Barros, Dayanne, Brasil, Larissa, Capella, Ana Greyce, Castro, Ramon, Costa, Erlane, de Souza, Dilcimar, Dias, Maianne, Dias, José, Ferreira, Klenilson, Figueiredo, Paula, Freitas, Thamires, Furtado, Ana Carolina, Gama, Larissa, Godinho, Vanessa, Gouy, Cintia, Hinojosa, Daniele, Jardim, Bruno, Jardim, Tyane, Junior, Joel, Lima, Augustto, Maia, Bernardo, Marins, Adriana, Mazurega, Kelry, Medeiros, Tercilene, Melo, Rosangela, Moraes, Marinete, Nascimento, Elizandra, Neves, Juliana, Oliveira, Maria Gabriela, Oliveira, Thais, Oliveira, Ingrid, Otsuka, Arthur, Paes, Rayssa, Pereira, Handerson, Pereira, Gabrielle, Prado, Christiane, Queiroz, Evelyn, Rodrigues, Laleyska, Rodrigues, Bebeto, Sampaio, Vanderson, Santos, Anna Gabriela, Santos, Daniel, Santos, Tilza, Santos, Evelyn, Sartim, Ariandra, Silva, Ana Beatriz, Silva, Juliana, Silva, Emanuelle, Simão, Mariana, Soares, Caroline, Sousa, Antonny, Trindade, Alexandre, Val, Fernando, Vasconcelos, Adria, Vasconcelos, Heline, Croda, Julio, Abreu, Carolinne, Almeida, Katya Martinez, Bitencourt de Andrade, Camila, Campos Angelo, Jhenyfer Thalyta, Gonçalvez de Araújo Arcanjo, Ghislaine, Silva Menezes Arruda, Bianca Maria, Ayala, Wellyngthon Espindola, Refosco Barbosa, Adelita Agripina, Vieira Batista, Felipe Zampieri, de Morais Batista, Fabiani, de Jesus Costa, Miriam, Croda, Mariana Garcia, Alves da Cruz, Lais, Pereira Diogo, Roberta Carolina, Dutra Escobar, Rodrigo Cezar, Fernandes, Iara Rodrigues, Figueiredo, Leticia Ramires, Cavalcanti Gonçalves, Leandro Galdino, Lahdo, Sarita, Lencina, Joyce dos Santos, Teodoro de Lima, Guilherme, Matos, Larissa Santos, Leopoldina Meireles, Bruna Tayara, Moreira, Debora Quadros, Silva Muranaka, Lilian Batista, de Oliveira, Adriely, Warszawski de Oliveira, Karla Regina, Vieira de Oliveira, Matheus, Dias de Oliveira, Roberto, Souza de Almeida dos Reis Pereira, Andrea Antonia, Puga, Marco, Ramos, Caroliny Veron, Souza da Rosa, Thaynara Haynara, Lopes dos Santos, Karla, Ribeiro dos Santos, Claudinalva, Leopoldina dos Santos, Dyenyffer Stéffany, Santos, Karina Marques, Pereira da Silva, Paulo César, Rocha da Silva, Paulo Victor, Silva, Débora dos Santos, Vieira da Silva, Patricia, Freitas da Rosa Soares, Bruno, Sperotto, Mariana Gazzoni, Tadokoro, Mariana Mayumi, Tsuha, Daniel, Ramos Vieira, Hugo Miguel, Pretti Dalcolmo, Margareth Maria, Lopes Alves da Paixão, Cíntia Maria, Corrêa E Castro, Gabriela, Collopy, Simone Silva, da Costa Silva, Renato, Almeida da Silveira, Samyra, Da-Cruz, Alda Maria, Maria da Silva Passos de Carvalho, Alessandra, de Cássia Batista, Rita, Silva De Freitas, Maria Luciana, Gerhardt de Oliveira Ferreira, Aline, Conceição de Souza, Ana Paula, Doblas, Paola Cerbino, Alcoforado da Silva dos Santos, Ayla, Cristine de Moraes dos Santos, Vanessa, Alves dos Santos Gomes, Dayane, Fortunato, Anderson Lage, Gomes-Silva, Adriano, Gonçalves, Monique Pinto, Garcia Meireless Junior, Paulo Leandro, Martins da Costa Carvalho, Estela, Motta, Fernando do Couto, Olivo de Mendonça, Ligia Maria, Pandine, Girlene dos Santos, Plácido Pereira, Rosa Maria, Maia, Ivan Ramos, Luiz da Rocha, Jorge, Paiva Romano, João Victor, Santos, Glauce dos, Fernandes da Silva, Erica, Mendonça Teixeira de Siqueira, Marilda Agudo, Prudêncio Soares, Ágatha Cristinne, Bonten, Marc, Arroyo, Sandra Franch, Besten, Henny Ophorst-den, Boon, Anna, Brakke, Karin M., Janssen, Axel, Koopmans, Marijke A.H., Lemmens, Toos, Leurink, Titia, Prat-Aymerich, Cristina, Septer-Bijleveld, Engelien, Stadhouders, Kimberly, Troeman, Darren, van der Waal, Marije, van Opdorp, Marjoleine, van Sluis, Nicolette, Wolters, Beatrijs, Kluytmans, Jan, Romme, Jannie, van den Bijllaardt, Wouter, van Mook, Linda, Rijen, M.M.L (Miranda) van, Filius, Margreet, Gisolf, Jet, Greven, Frances, Huijbens, Danique, Hassing, Robert Jan, Pon, Roos, Preijers, Lieke, van Leusen, Joke, Verheij, Harald, Boersma, Wim, Brans, Evelien, Kloeg, Paul, Molenaar-Groot, Kitty, Nguyen, Nhat Khanh, Paternotte, Nienke, Rol, Anke, Stooper, Lida, Dijkstra, Helga, Eggenhuizen, Esther, Huijs, Lucas, Moorlag, Simone, Netea, Mihai, Pranger, Eva, Taks, Esther, Oever, Jaap ten, Heine, Rob ter, Blauwendraat, Kitty, Meek, Bob, Erkaya, Isil, Harbech, Houda, Roescher, Nienke, Peeters, Rifka, Riele, Menno te, Zhou, Carmen, Calbo, Esther, Marti, Cristina Badia, Palomares, Emma Triviño, Porcuna, Tomás Perez, Barriocanal, Anabel, Barriocanal, Ana Maria, Casas, Irma, Dominguez, Jose, Esteve, Maria, Lacoma, Alicia, Latorre, Irene, Molina, Gemma, Molina, Barbara, Rosell, Antoni, Vidal, Sandra, Barrera, Lydia, Bustos, Natalia, Calderón, Ines Portillo, Campos, David Gutierrez, Carretero, Jose Manuel, Castellano, Angel Dominguez, Compagnone, Renato, Ramirez de Arellano, Encarnacion, Serna, Almudena de la, Dolores del Toro Lopez, Maria, Clement Espindola, Marie-Alix, Martin Gutierrez, Ana Belen, Hernandez, Alvaro Pascual, Jiménez, Virginia Palomo, Moreno, Elisa, Navarrete, Nicolas, Paño, Teresa Rodriguez, Rodríguez-Baño, Jesús, Tristán, Enriqueta, Rios Villegas, Maria Jose, Garces, Atsegiñe Canga, Amo, Erika Castro, Guerrero, Raquel Coya, Goikoetxea, Josune, Jorge, Leticia, Perez, Cristina, Fariñas Álvarez, María Carmen, Cuadra, Manuel Gutierrez, Arnaiz de las Revillas Almajano, Francisco, Garcia, Pilar Bohedo, Poderos, Teresa Giménez, Rico, Claudia González, Sanchez, Blanca, Valero, Olga, Vega, Noelia, Campbell, John, Barnes, Anna, Catterick, Helen, Cranston, Tim, Dawe, Phoebe, Fletcher, Emily, Fouracre, Liam, Gifford, Alison, Kirkwood, John, Martin, Christopher, McAnew, Amy, Mitchell, Marcus, Newman, Georgina, O’Connell, Abby, Onysk, Jakob, Quinn, Lynne, Rhodes, Shelley, Stone, Samuel, Symons, Lorrie, Tripp, Harry, Warris, Adilia, Watkins, Darcy, Whale, Bethany, Harding, Alex, Lockhart, Gemma, Sidaway-Lee, Kate, Hilton, Sam, Manton, Sarah, Webber-Rookes, Daniel, Winder, Rachel, Moore, James, Bateman, Freya, Gibbons, Michael, Knight, Bridget, Moss, Julie, Statton, Sarah, Studham, Josephine, Hall, Lydia, Moyle, Will, Venton, Tamsin, Messina, Nicole L., Grubor-Bauk, Branka, Lynn, David J., Perrett, Kirsten P., Pittet, Laure F., Rudraraju, Rajeev, Stevens, Natalie E., and Subbarao, Kanta
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- 2024
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3. Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study.
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Osowicki, Joshua, Azzopardi, Kristy I., Baker, Ciara, Waddington, Claire S., Pandey, Manisha, Schuster, Tibor, Grobler, Anneke, Cheng, Allen C., Pollard, Andrew J., McCarthy, James S., Good, Michael F., Walker, Mark J., Dale, James B., Batzloff, Michael R., Carapetis, Jonathan R., Smeesters, Pierre R., and Steer, Andrew C.
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STREPTOCOCCUS pyogenes , *HUMAN experimentation , *STREPTOCOCCUS , *CURRENT good manufacturing practices , *VACCINATION - Abstract
Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a diverse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease. We review the small number of historical GAS HIS and present the study protocol for a dose-ranging inpatient study in healthy adults. The primary objective of the study is to establish a new GAS pharyngitis HIS with an attack rate of at least 60% as a safe and reliable platform for vaccine evaluation and pathogenesis research. According to an adaptive dose-ranging study design, emm 75 GAS doses manufactured in keeping with principles of Good Manufacturing Practice will be directly applied by swab to the pharynx of carefully screened healthy adult volunteers at low risk of severe complicated GAS disease. Participants will remain as closely monitored inpatients for up to six days, observed for development of the primary outcome of acute symptomatic pharyngitis, as defined by clinical and microbiological criteria. All participants will be treated with antibiotics and followed as outpatients for six months. An intensive sampling schedule will facilitate extensive studies of host and organism dynamics during experimental pharyngitis. Ethics approval has been obtained and the study has been registered at ClinicalTrials.gov (NCT03361163). [ABSTRACT FROM AUTHOR]
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- 2019
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4. A totally synthetic lipopeptide-based self-adjuvanting vaccine induces neutralizing antibodies against heat-stable enterotoxin from enterotoxigenic Escherichia coli
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Zeng, Weiguang, Azzopardi, Kristy, Hocking, Dianna, Wong, Chinn Yi, Robevska, Gorjana, Tauschek, Marija, Robins-Browne, Roy M., and Jackson, David C.
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ENTEROTOXINS , *ESCHERICHIA coli , *TOLL-like receptors , *CYSTEINE , *INTRANASAL medication , *LABORATORY mice - Abstract
Abstract: ST-based lipopeptide vaccine candidates were constructed in which ST was chemically synthesized and folded into the correct conformation prior to ligation to a module containing a T-helper cell epitope (TH) and the Toll-like receptor 2 (TLR2) agonist, S-[2,3-bis(palmitoyloxy)propyl]cysteine (P2C). Two different chemistries, thioether-based and oxime-based, were then used to ligate ST to the lipidated TH epitope. The enterotoxic activity of synthetic ST and the ST-based lipopeptide vaccines was determined in mice followed by an evaluation of immunological efficacy. The importance of the fine detail in chemical composition used in vaccine design was demonstrated by the findings that (i) the oxime-based vaccine exhibited little or no toxicity but the thioether-based vaccine, exhibited residual toxicity in suckling mice, (ii) although each of the synthetic vaccines generated specific anti-ST antibodies, it was the low titer antibodies induced by the oxime-based vaccine that demonstrated better neutralizing activity suggesting that the chemical linkage also affects the specificity of antibodies, (iii) the geometric arrangement of ST within a vaccine can profoundly affect the specificity and biological function of the antibodies that are elicited, and (iv) the lipopeptide-based ST vaccine candidate assembled using oxime chemistry induced a better neutralizing antibody response to ST when administered by the mucosal (intranasal) route. [Copyright &y& Elsevier]
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- 2012
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5. Liposomal phospholipid preparations of chloramphenicol for ophthalmic applications.
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Mahmoud, Sherif S., Gehman, John D., Azzopardi, Kristy, Robins-Browne, Roy M., and Separovic, Frances
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LIPOSOMES , *PHOSPHOLIPIDS , *BILAYER lipid membranes , *CHLORAMPHENICOL , *STAPHYLOCOCCUS , *BACTERIAL diseases , *STAPHYLOCOCCUS aureus infections - Abstract
Since their discovery by Bangham and coworkers almost four decades ago, liposomes have become models for biomembranes and vehicles for pharmaceutical, diagnostic, and cosmetic agents. One of the advantages of using liposomes as a drug vehicle is their ability for slow release, thus reducing dosage, localizing a drug, and minimizing its side-effects. Antibiotic resistance is a growing global problem, including for ocular bacterial infection by Staphylococcus aureus, where time is an important parameter that determines the severity of infection. This situation has prompted the pursuit of ways to prepare drug-encapsulating liposomes that enable bulk release of the drug chloramphenicol (CAP) once the liposomal structure is perturbed. Our approach is a two-step process: first, to characterize the interaction of CAP with model biomembranes of dimyristoylphosphatidylcholine (DMPC) used to prepare CAP-liposomes by different formulations; second, to test the efficiency of these formulation against S. aureus. Solid-state NMR, differential scanning calorimetry, and infrared spectroscopy were used to study the interaction of CAP with DMPC bilayers. The minimum inhibitory concentrations and time-kill curves for S. aureus using different liposomal preparations were compared. Evidence of conformational changes in the DMPC molecules and the effectiveness of the CAP encapsulated in liposomes are reported. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2691–2701, 2008 [ABSTRACT FROM AUTHOR]
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- 2008
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6. Meningitis in children in Fiji: etiology, epidemiology, and neurological sequelae
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Biaukula, Viema Lewagalu, Tikoduadua, Lisi, Azzopardi, Kristy, Seduadua, Anna, Temple, Beth, Richmond, Peter, Robins-Browne, Roy, Mulholland, Edward Kim, and Russell, Fiona Mary
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MENINGITIS in children , *ETIOLOGY of diseases , *EPIDEMIOLOGY , *QUALITY of life , *STREPTOCOCCUS , *BLOOD testing , *CEREBROSPINAL fluid - Abstract
Summary: Objectives: To describe the etiology, epidemiology, neurological sequelae, and quality of life of children aged 1 month to less than 5 years admitted with meningitis to the Colonial War Memorial Hospital (CWMH), Suva, Fiji. Methods: Over a 3-year period, all eligible children with suspected meningitis admitted to CWMH had blood drawn for culture. Of these children, those for whom is was possible were tested for a four-fold rise in antibody titers to Haemophilus influenzae type b (Hib) and pneumococcal surface adhesin A (PsaA). Cerebrospinal fluid (CSF) was taken for bacteriological culture and antigen testing. CSF was also tested by PCR for Streptococcus species, Neisseria meningitidis, Hib, Mycobacterium tuberculosis, and enterovirus. Pneumococcal isolates were serotyped using multiplex-PCR reverse-line blot hybridization. Following discharge, cases underwent a neurological assessment, audiometry, and quality of life assessment (Pediatric Quality of Life Inventory (PedsQL) tool). Results: There were 70 meningitis cases. Meningitis was more common in indigenous Fijian than Indo-Fijian children. Enterovirus was the most common etiological agent and appeared to be outbreak-associated. Streptococcus pneumoniae was the most common bacterial cause of meningitis with an annual incidence of 9.9 per 100 000 under 5 years old (95% confidence interval 4.9–17.7) and a case fatality rate of 36%. With the exception of deafness, neurological sequelae were more frequent in cases of bacterial meningitis than in viral meningitis (18.5% vs. 0%, p =0.04). Quality of life at follow-up was significantly lower in patients with bacterial meningitis than in those with viral meningitis (p =0.003) or meningitis of unknown etiology (p =0.004). Conclusions: During the study period an outbreak of enterovirus occurred making it the most common etiological agent identified. However in the absence of this outbreak, S. pneumoniae was the most common cause of childhood meningitis in Fiji. Bacterial meningitis is associated with serious sequelae and a reduced quality of life. [Copyright &y& Elsevier]
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- 2012
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7. A Modular Approach to Assembly of Totally Synthetic Self-adjuvanting Lipopeptide-based Vaccines Allows Conformational Epitope Building.
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Weiguang Zeng, Horrocks, Kylie J., Robevska, Gorjana, Chinn Yi Wong, Azzopardi, Kristy, Tauschek, Marija, Robins-Browne, Roy M., and Jackson, David C.
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SYNTHETIC vaccines , *EPITOPES , *AMINO acid sequence , *CELLULAR immunity , *ESCHERICHIA coli , *INFLUENZA vaccines , *ENTEROTOXINS , *T cells - Abstract
The technology described here allows the chemical synthesis of vaccines requiring correctly folded epitopes and that contain difficult or long peptide sequences. The final self-adjuvanting product promotes strong humoral and/or cell-mediated immunity. A module containing common components of the vaccine (T helper cell epitope and the adjuvanting lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine) was assembled to enable a plug and play approach to vaccine assembly. The inclusion within the module of a chemical group with chemical properties complementary and orthogonal to a chemical group present in the target epitope allowed chemoselective ligation of the two vaccine components. The heat-stable enterotoxin of enterotoxigenic Escherichia coil that requires strict conformational integrity for biological activity and the reproductive hormone luteinizing hormone-releasing hormone were used as the target epitopes for the antibody vaccines. An epitope from the acid polymerase of influenza virus was used to assemble a CD8+ T cell vaccine. Evaluation of each vaccine candidate in animals demonstrated the feasibility of the approach and that the type of immune response required, viz, antibody or cytotoxic T lymphocyte, dictates the nature of the chemical linkage between the module and target epitope. The use of a thioether bond between the module and target epitope had little or no adverse effect on antibody responses, whereas the use of a disulfide bond between the module and target epitope almost completely abrogated the antibody response. In contrast, better cytotoxic T lymphocyte responses were obtained when a disulfide bond was used. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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