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1. Superior efficacy of a skin-applied microprojection device for delivering a novel Zika DNA vaccine.

Author

Masavuli, Makutiro, Young, Paul, Gowans, Eric, Grubor-Bauk, Branka, Muller, David, Wijesundara, Danushka, Yeow, Arthur, McMillan, Christopher, Choo, Jovin, Todorovic, Aleksandra, and Mekonnen, Zelalem

Subjects
DNA vaccine, HD-MAP, MT: Delivery Strategies, T cell immunity, Zika, cytotoxic T cells, microneedle, non-structural protein 1, skin patch
Abstract

Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine.

Published
2023

2. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Author

Ryan, Feargal J, Hope, Christopher M, Masavuli, Makutiro G, Lynn, Miriam A, Mekonnen, Zelalem A, Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O’Connor, Stephanie, Reddi, Benjamin AJ, Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M, Beard, Michael R, Barry, Simon C, Grubor-Bauk, Branka, and Lynn, David J

Subjects
Emerging Infectious Diseases, Vaccine Related, Pneumonia & Influenza, Lung, Pneumonia, Prevention, Infectious Diseases, Genetics, Biodefense, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Antibodies, Viral, COVID-19, Humans, Immune System, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Immunity, RNA-Seq, T cell, Antibody responses, Convalescent patients, Immunophenotyping, Long COVID, Post-acute sequelae of COVID-19, Post COVID-19 condition, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.MethodsWe have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.ResultsAnti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.ConclusionsVariation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

Published
2022

3. SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

Author

Garcia-Valtanen, Pablo, Hope, Christopher M, Masavuli, Makutiro G, Yeow, Arthur Eng Lip, Balachandran, Harikrishnan, Mekonnen, Zelalem A, Al-Delfi, Zahraa, Abayasingam, Arunasingam, Agapiou, David, Stella, Alberto Ospina, Aggarwal, Anupriya, Bouras, George, Gummow, Jason, Ferguson, Catherine, O’Connor, Stephanie, McCartney, Erin M, Lynn, David J, Maddern, Guy, Gowans, Eric J, Reddi, Benjamin AJ, Shaw, David, Kok-Lim, Chuan, Beard, Michael R, Weiskopf, Daniela, Sette, Alessandro, Turville, Stuart G, Bull, Rowena A, Barry, Simon C, and Grubor-Bauk, Branka

Subjects
Infectious Diseases, Pneumonia & Influenza, Pneumonia, Prevention, Biodefense, Lung, Immunization, Vaccine Related, Emerging Infectious Diseases, Infection, Good Health and Well Being, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Humans, Reinfection, SARS-CoV-2, Spike Glycoprotein, Coronavirus, T-Lymphocytes, T cell immunity, Variant of Concern, antibody response, antigen drift, memory B cells, virus neutralization
Abstract

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.

Published
2022

4. Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines—an exploratory sub-study of the BRACE trial

Author

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

Published
2024
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5. Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities

Author

Zhang, Wuji, Kedzierski, Lukasz, Chua, Brendon Y., Mayo, Mark, Lonzi, Claire, Rigas, Vanessa, Middleton, Bianca F., McQuilten, Hayley A., Rowntree, Louise C., Allen, Lilith F., Purcell, Ruth A., Tan, Hyon-Xhi, Petersen, Jan, Chaurasia, Priyanka, Mordant, Francesca, Pogorelyy, Mikhail V., Minervina, Anastasia A., Crawford, Jeremy Chase, Perkins, Griffith B., Zhang, Eva, Gras, Stephanie, Clemens, E. Bridie, Juno, Jennifer A., Audsley, Jennifer, Khoury, David S., Holmes, Natasha E., Thevarajan, Irani, Subbarao, Kanta, Krammer, Florian, Cheng, Allen C., Davenport, Miles P., Grubor-Bauk, Branka, Coates, P. Toby, Christensen, Britt, Thomas, Paul G., Wheatley, Adam K., Kent, Stephen J., Rossjohn, Jamie, Chung, Amy W., Boffa, John, Miller, Adrian, Lynar, Sarah, Nelson, Jane, Nguyen, Thi H. O., Davies, Jane, and Kedzierska, Katherine

Published
2023
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7. Enhanced T Cell Responses Induced by a Necrotic Dendritic Cell Vaccine, Expressing HCV NS3

Author

Mekonnen, Zelalem A, Masavuli, Makutiro G, Yu, Wenbo, Gummow, Jason, Whelan, Dawn M, Al-Delfi, Zahraa, Torresi, Joseph, Gowans, Eric J, and Grubor-Bauk, Branka

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Digestive Diseases, Prevention, Vaccine Related, Immunization, Emerging Infectious Diseases, Hepatitis - C, Hepatitis, Chronic Liver Disease and Cirrhosis, Infectious Diseases, HIV/AIDS, Biotechnology, Liver Disease, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Inflammatory and immune system, Infection, Good Health and Well Being, necrosis, HCV, cell mediated immunity, cross presentation, vaccine, hepatitis (C) virus, Environmental Science and Management, Soil Sciences, Microbiology, Medical microbiology
Abstract

A vaccine that induces potent, broad and sustained cell-mediated immunity, resulting in effective memory has the potential to restrict hepatitis C (HCV) virus infection. Early, multi-functional CD4+ and CD8+ T cell responses against non-structural protein 3 (NS3) have been associated with HCV clearance. Necrotic cells generate strong immune responses and represent a major antigenic source used by dendritic cells (DC) for processing and presentation, but there is conflicting evidence as to their immunogenicity in vaccination. Immunization with DC loaded with viral antigens has been done in the past, but to date the immunogenicity of live vs. necrotic DC vaccines has not been investigated. We developed a DC2.4 cell line stably expressing HCV NS3, and compared the NS3-specific responses of live vs. necrotic NS3 DC. Vaccination of mice with necrotic NS3 DC increased the breadth of T-cell responses and enhanced the production of IL-2, TNF-α, and IFN-γ by effector memory CD4+ and CD8+T cells, compared to mice vaccinated with live NS3 DC. A single dose of necrotic NS3 DC vaccine induced a greater influx and activation of cross-presenting CD11c+ CD8α+ DC and necrosis-sensing Clec9A+ DC in the draining lymph nodes. Furthermore, using a hydrodynamic challenge model necrotic NS3 DC vaccination resulted in enhanced clearance of NS3-positive hepatocytes from the livers of vaccinated mice. Taken together, the data demonstrate that necrotic DC represent a novel and exciting vaccination strategy capable of inducing broad and multifunctional T cell memory.

Published
2020

8. A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines

Author

Ryan, Feargal J., Norton, Todd S., McCafferty, Conor, Blake, Stephen J., Stevens, Natalie E., James, Jane, Eden, Georgina L., Tee, Yee C., Benson, Saoirse C., Masavuli, Makutiro G., Yeow, Arthur E.L., Abayasingam, Arunasingam, Agapiou, David, Stevens, Hannah, Zecha, Jana, Messina, Nicole L., Curtis, Nigel, Ignjatovic, Vera, Monagle, Paul, Tran, Huyen, McFadyen, James D., Bull, Rowena A., Grubor-Bauk, Branka, Lynn, Miriam A., Botten, Rochelle, Barry, Simone E., and Lynn, David J.

Published
2023
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9. Single-Dose Vaccination with a Hepatotropic Adeno-associated Virus Efficiently Localizes T Cell Immunity in the Liver with the Potential To Confer Rapid Protection against Hepatitis C Virus.

Author

Mekonnen, Zelalem A, Grubor-Bauk, Branka, English, Kieran, Leung, Preston, Masavuli, Makutiro G, Shrestha, Ashish C, Bertolino, Patrick, Bowen, David G, Lloyd, Andrew R, Gowans, Eric J, and Wijesundara, Danushka K

Subjects
DNA vaccine, adeno-associated virus vaccine, cytotoxic T cells, helper T cells, hepatitis C virus vaccine, liver immunity, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

Hepatitis C virus (HCV) is a significant contributor to the global disease burden, and development of an effective vaccine is required to eliminate HCV infections worldwide. CD4+ and CD8+ T cell immunity correlates with viral clearance in primary HCV infection, and intrahepatic CD8+ tissue-resident memory T (TRM) cells provide lifelong and rapid protection against hepatotropic pathogens. Consequently, we aimed to develop a vaccine to elicit HCV-specific CD4+ and CD8+ T cells, including CD8+ TRM cells, in the liver, given that HCV primarily infects hepatocytes. To achieve this, we vaccinated wild-type BALB/c mice with a highly immunogenic cytolytic DNA vaccine encoding a model HCV (genotype 3a) nonstructural protein (NS5B) and a mutant perforin (pVAX-NS5B-PRF), as well as a recombinant adeno-associated virus (AAV) encoding NS5B (rAAV-NS5B). A novel fluorescent target array (FTA) was used to map immunodominant CD4+ T helper (TH) cell and cytotoxic CD8+ T cell epitopes of NS5B in vivo, which were subsequently used to design a KdNS5B451-459 tetramer and analyze NS5B-specific T cell responses in vaccinated mice in vivo The data showed that intradermal prime/boost vaccination with pVAX-NS5B-PRF was effective in eliciting TH and cytotoxic CD8+ T cell responses and intrahepatic CD8+ TRM cells, but a single intravenous dose of hepatotropic rAAV-NS5B was significantly more effective. As a T-cell-based vaccine against HCV should ideally result in localized T cell responses in the liver, this study describes primary observations in the context of HCV vaccination that can be used to achieve this goal.IMPORTANCE There are currently at least 71 million individuals with chronic HCV worldwide and almost two million new infections annually. Although the advent of direct-acting antivirals (DAAs) offers highly effective therapy, considerable remaining challenges argue against reliance on DAAs for HCV elimination, including high drug cost, poorly developed health infrastructure, low screening rates, and significant reinfection rates. Accordingly, development of an effective vaccine is crucial to HCV elimination. An HCV vaccine that elicits T cell immunity in the liver will be highly protective for the following reasons: (i) T cell responses against nonstructural proteins of the virus are associated with clearance of primary infection, and (ii) long-lived liver-resident T cells alone can protect against malaria infection of hepatocytes. Thus, in this study we exploit promising vaccination platforms to highlight strategies that can be used to evoke highly functional and long-lived T cell responses in the liver for protection against HCV.

Published
2019

10. Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines.

Author

Shrestha, Ashish C, Wijesundara, Danushka K, Masavuli, Makutiro G, Mekonnen, Zelalem A, Gowans, Eric J, and Grubor-Bauk, Branka

Subjects
DNA vaccine, HCV, HIV, adjuvants, bicistronic, cytolytic, perforin, plasmid, vaccine delivery
Abstract

DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines.

Published
2019

11. Toward DNA-Based T-Cell Mediated Vaccines to Target HIV-1 and Hepatitis C Virus: Approaches to Elicit Localized Immunity for Protection.

Author

Mekonnen, Zelalem A, Grubor-Bauk, Branka, Masavuli, Makutiro G, Shrestha, Ashish C, Ranasinghe, Charani, Bull, Rowena A, Lloyd, Andrew R, Gowans, Eric J, and Wijesundara, Danushka K

Subjects
DNA vaccine, HCV, HIV/AIDS, T cell immunity, hepatitis C, human immunodeficiency virus, tissue-resident memory, Drug Discovery, HIV Infections, Hepatitis C, Humans, T-Lymphocytes, Vaccines, DNA, Vaccinology, Viral Vaccines, Vaccines, DNA, Biochemistry and Cell Biology, Microbiology
Abstract

Human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) are major contributors to the global disease burden with many experts recognizing the requirement of an effective vaccine to bring a durable end to these viral epidemics. The most promising vaccine candidates that have advanced into pre-clinical models and the clinic to eliminate or provide protection against these chronic viruses are viral vectors [e.g., recombinant cytomegalovirus, Adenovirus, and modified vaccinia Ankara (MVA)]. This raises the question, is there a need to develop DNA vaccines against HIV-1 and HCV? Since the initial study from Wolff and colleagues which showed that DNA represents a vector that can be used to express transgenes durably in vivo, DNA has been regularly evaluated as a vaccine vector albeit with limited success in large animal models and humans. However, several recent studies in Phase I-IIb trials showed that vaccination of patients with recombinant DNA represents a feasible therapeutic intervention to even cure cervical cancer, highlighting the potential of using DNA for human vaccinations. In this review, we will discuss the limitations and the strategies of using DNA as a vector to develop prophylactic T cell-mediated vaccines against HIV-1 and HCV. In particular, we focus on potential strategies exploiting DNA vectors to elicit protective localized CD8+ T cell immunity in the liver for HCV and in the cervicovaginal mucosa for HIV-1 as localized immunity will be an important, if not critical component, of an efficacious vaccine against these viral infections.

Published
2019

12. Rapamycin and inulin for booster vaccine response stimulation (RIVASTIM)—rapamycin: study protocol for a randomised, controlled trial of immunosuppression modification with rapamycin to improve SARS-CoV-2 vaccine response in kidney transplant recipients

Author

Tunbridge, Matthew, Perkins, Griffith B., Singer, Julian, Salehi, Tania, Ying, Tracey, Grubor-Bauk, Branka, Barry, Simon, Sim, Beatrice, Hissaria, Pravin, Chadban, Steven J., and Coates, P. Toby

Published
2022
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13. Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes

Author

Sinclair, Jane, primary, Vedelago, Courtney, additional, Ryan, Feargal, additional, Carney, Meagan, additional, Redd, Meredith, additional, Lynn, Miriam, additional, Grubor-Bauk, Branka, additional, Cao, Yuanzhao, additional, Henders, Anjali, additional, Chew, Keng Yih, additional, Gilroy, Deborah, additional, Greaves, Kim, additional, Labzin, Larisa, additional, Ziser, Laura, additional, Ronacher, Katharina, additional, Wallace, Leanne, additional, Zhang, Yiwen, additional, Macauslane, Kyle, additional, Ellis, Daniel, additional, Rao, Sudha, additional, Burr, Lucy, additional, Bain, Amanda, additional, Schulz, Benjamin L., additional, Li, Junrong, additional, Lynn, David J., additional, Palpant, Nathan, additional, Wuethrich, Alain, additional, Trau, Matt, additional, and Short, Kirsty, additional

Published
2024
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15. Dietary Inulin to Improve SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients: The RIVASTIM-Inulin Randomised Controlled Trial.

Author

Singer, Julian, Tunbridge, Matthew J., Shi, Bree, Perkins, Griffith B., Chai, Cheng Sheng, Salehi, Tania, Sim, Beatrice Z., Kireta, Svjetlana, Johnston, Julie K., Akerman, Anouschka, Milogiannakis, Vanessa, Aggarwal, Anupriya, Turville, Stuart, Hissaria, Pravin, Ying, Tracey, Wu, Huiling, Grubor-Bauk, Branka, Coates, P. Toby, and Chadban, Steven J.

Subjects
VACCINE effectiveness, COVID-19 vaccines, KIDNEY transplantation, INULIN, SHORT-chain fatty acids
Abstract

Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as Bifidobacterium associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut Bifidobacterium, as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Immune profiling of COVID-19 vaccine responses in people with multiple sclerosis on B cell-depleting therapy

Author

Perkins, Griffith B., primary, Hope, Christopher M., additional, Chai, Cheng Sheng, additional, Tunbridge, Matthew J., additional, Sterling, Sebastian, additional, Webb, Kevin, additional, Yap, Joey, additional, Yeow, Arthur Eng Lip, additional, Masavuli, Makutiro G., additional, Kireta, Svjetlana, additional, Zuiani, James D., additional, Akerman, Anouschka, additional, Aggarwal, Anupriya, additional, Milogiannakis, Vanessa, additional, Roberts, Matthew B., additional, Wilson, William, additional, Hurtado, Plinio R., additional, Turville, Stuart, additional, Grubor-Bauk, Branka, additional, Barry, Simon C., additional, Coates, P. Toby, additional, Ravindran, Janakan, additional, and Hissaria, Pravin, additional

Published
2023
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17. Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma

Author

Williams, Connor M. D., primary, Noll, Jacqueline E., additional, Bradey, Alanah L., additional, Duggan, Jvaughn, additional, Wilczek, Vicki J., additional, Masavuli, Makutiro G., additional, Grubor‐Bauk, Branka, additional, Panagopoulos, Romana A., additional, Hewett, Duncan R., additional, Mrozik, Krzysztof M., additional, Zannettino, Andrew C. W., additional, Vandyke, Kate, additional, and Panagopoulos, Vasilios, additional

Published
2023
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19. Longitudinal Characterization of Phagocytic and Neutralization Functions of Anti-Spike Antibodies in Plasma of Patients after Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Author

Adhikari, Anurag, primary, Abayasingam, Arunasingam, additional, Rodrigo, Chaturaka, additional, Agapiou, David, additional, Pandzic, Elvis, additional, Brasher, Nicholas A., additional, Fernando, Bentotage Samitha Madushan, additional, Keoshkerian, Elizabeth, additional, Li, Hui, additional, Kim, Ha Na, additional, Lord, Megan, additional, Popovic, Gordona, additional, Rawlinson, William, additional, Mina, Michael, additional, Post, Jeffrey J., additional, Hudson, Bernard, additional, Gilroy, Nicky, additional, Dwyer, Dominic, additional, Sasson, Sarah C., additional, Grubor-Bauk, Branka, additional, Lloyd, Andrew R., additional, Martinello, Marianne, additional, Bull, Rowena A., additional, and Tedla, Nicodemus, additional

Published
2022
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20. A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

Author

Ryan, Feargal J., primary, Norton, Todd S., additional, McCafferty, Conor, additional, Blake, Stephen J., additional, Stevens, Natalie E., additional, James, Jane, additional, Eden, Georgina L., additional, Tee, Yee C., additional, Benson, Saoirse C., additional, Masavuli, Makutiro G., additional, Yeow, Arthur EL, additional, Abayasingam, Arunasingam, additional, Agapiou, David, additional, Stevens, Hannah, additional, Zecha, Jana, additional, Messina, Nicole L., additional, Curtis, Nigel, additional, Ignjatovic, Vera, additional, Monagle, Paul, additional, Tran, Huyen, additional, McFadyen, James D., additional, Bull, Rowena A., additional, Grubor-Bauk, Branka, additional, Lynn, Miriam A., additional, Botten, Rochelle, additional, Barry, Simone E., additional, and Lynn, David J., additional

Published
2022
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23. Concurrent vaccination of kidney transplant recipients and close household cohabitants against COVID-19

Author

Perkins, Griffith B., primary, Tunbridge, Matthew, additional, Salehi, Tania, additional, Chai, Cheng Sheng, additional, Kireta, Svjetlana, additional, Johnston, Julie, additional, Penko, Daniella, additional, Nitschke, Jodie, additional, Yeow, Arthur Eng Lip, additional, Al-Delfi, Zahraa, additional, Drogemuller, Christopher J., additional, Garcia-Valtanen, Pablo, additional, Masavuli, Makutiro G., additional, Hope, Christopher M., additional, Singer, Julian, additional, Aggarwal, Anupriya, additional, Ospina Stella, Alberto, additional, Turville, Stuart G., additional, Hurtado, Plinio R., additional, Barry, Simon C., additional, Hissaria, Pravin, additional, Grubor-Bauk, Branka, additional, Chadban, Steven J., additional, and Coates, P. Toby, additional

Published
2022
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24. Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses

Author

Balachandran, Harikrishnan, primary, Phetsouphanh, Chansavath, additional, Agapiou, David, additional, Adhikari, Anurag, additional, Rodrigo, Chaturaka, additional, Hammoud, Mohamed, additional, Shrestha, Lok Bahadur, additional, Keoshkerian, Elizabeth, additional, Gupta, Money, additional, Turville, Stuart, additional, Christ, Daniel, additional, King, Cecile, additional, Sasson, Sarah C., additional, Bartlett, Adam, additional, Grubor-Bauk, Branka, additional, Rawlinson, William, additional, Aggarwal, Anupriya, additional, Stella, Alberto Ospina, additional, Klemm, Vera, additional, Mina, Michael M., additional, Post, Jeffrey J., additional, Hudson, Bernard, additional, Gilroy, Nicky, additional, Konecny, Pam, additional, Ahlenstiel, Golo, additional, Dwyer, Dominic E., additional, Sorrell, Tania C., additional, Kelleher, Anthony, additional, Tedla, Nicodemus, additional, Lloyd, Andrew R., additional, Martinello, Marianne, additional, and Bull, Rowena A., additional

Published
2022
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25. Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses

Author

Balachandran, Harikrishnan, Phetsouphanh, Chansavath, Agapiou, David, Adhikari, Anurag, Rodrigo, Chaturaka, Hammoud, Mohamed, Shrestha, Lok Bahadur, Keoshkerian, Elizabeth, Gupta, Money, Turville, Stuart, Christ, Daniel, King, Cecile, Sasson, Sarah C., Bartlett, Adam, Grubor-Bauk, Branka, Rawlinson, William, Aggarwal, Anupriya, Stella, Alberto Ospina, Klemm, Vera, Mina, Michael M., Post, Jeffrey J., Hudson, Bernard, Gilroy, Nicky, Konecny, Pam, Ahlenstiel, Golo, Dwyer, Dominic E., Sorrell, Tania C., Kelleher, Anthony, Tedla, Nicodemus, Lloyd, Andrew R., Martinello, Marianne, Bull, Rowena A., and Group, COSIN Study

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Delta variant, QH301-705.5, SARS-CoV-2 OX40 CD4 T cell assay, Antibodies, Viral, variants of concern, Severity of Illness Index, Article, General Biochemistry, Genetics and Molecular Biology, protection efficacy prediction, Cohort Studies, Memory B Cells, Humans, Biology (General), SARS-CoV-2, Australia, Immunity, RBD-specific memory B cells longevity, COVID-19, SARS-CoV-2 antibody duration, Antibodies, Neutralizing, 12 months after SARS-CoV-2 infection, Immunity, Humoral, Coronavirus, SARS-CoV-2 neutralization, Spike Glycoprotein, Coronavirus, Female, Broadly Neutralizing Antibodies
Abstract

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%–76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection., Graphical abstract, One year after SARS-CoV-2 infection, despite declining antibody titers, Balachandran et al. report a disease-severity-associated maintenance of antibody functions and memory B cell magnitudes. The convalescent serum could neutralize most VOCs, and the initial CD4 T cell levels predict the antibody neutralization breadth and memory B cell durability.

Published
2022

26. Additional file 10 of Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Author

Ryan, Feargal J., Hope, Christopher M., Masavuli, Makutiro G., Lynn, Miriam A., Mekonnen, Zelalem A., Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O���Connor, Stephanie, Reddi, Benjamin A. J., Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M., Beard, Michael R., Barry, Simon C., Grubor-Bauk, Branka, and Lynn, David J.

Abstract

Additional file 10. Symptom questionnaire sent to patients to assess presence of long COVID associated symptoms.

Published
2022
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27. Additional file 3 of Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Author

Ryan, Feargal J., Hope, Christopher M., Masavuli, Makutiro G., Lynn, Miriam A., Mekonnen, Zelalem A., Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O���Connor, Stephanie, Reddi, Benjamin A. J., Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M., Beard, Michael R., Barry, Simon C., Grubor-Bauk, Branka, and Lynn, David J.

Abstract

Additional file 3: Figure S3: Adjusting for differences in immune cell populations. We repeated the differential expression analysis multiple times, each time adjusting for differences in the frequency of major immune cell populations among individuals. Each panel shows the enrichment of selected pathways (same as those shown in Fig. 4F) among genes identified as being significantly up-regulated in each analysis (FDR 1.25-fold). None = no immune cell population adjustment.

Published
2022
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28. Additional file 2 of Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Author

Ryan, Feargal J., Hope, Christopher M., Masavuli, Makutiro G., Lynn, Miriam A., Mekonnen, Zelalem A., Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O���Connor, Stephanie, Reddi, Benjamin A. J., Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M., Beard, Michael R., Barry, Simon C., Grubor-Bauk, Branka, and Lynn, David J.

Abstract

Additional file 2: Figure S2: Expression of genes in two pathways identified as downregulated in COVID-19 convalescents and healthy controls. (A) Reactome pathway R-HSA-76002 ���Platelet activation, signaling and aggregation��� and (B) KEGG pathway hsa00190 ���Oxidative phosphorylation���. Oxidative phosphorylation genes are sub-divided into nuclear and mitochondrially encoded, with the same x axis order of samples in each panel. Only differentially expressed genes (FDR 1.25-fold) within each pathway are shown. (C) Serum CRP levels in samples collected from healthy controls (HC) and COVID-19 convalescent individuals at 12, 16 and 24 weeks post infection.

Published
2022
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29. Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.

Author

Adhikari, Anurag, primary, Abayasingam, Arunasingam, additional, Rodrigo, Chaturaka, additional, Agapiou, David, additional, Pandzic, Elvis, additional, Brasher, Nicholas A, additional, Fernando, Bentotage Samitha Madushan, additional, Keoshkerian, Elizabeth, additional, Li, Hui, additional, Kim, Ha Na, additional, Lord, Megan, additional, Popovic, Gordona, additional, Rawlinson, William, additional, Mina, Michael, additional, Post, Jeffrey J, additional, Hudson, Bernard, additional, Gilroy, Nicole, additional, Bartlett, Adam W., additional, Ahlenstiel, Golo, additional, Grubor-Bauk, Branka, additional, Dwyer, Dominic, additional, Konecny, Pamela, additional, Lloyd, Andrew R, additional, Martinello, Marianne, additional, Bull, Rowena A, additional, and Tedla, Nicodemus, additional

Published
2021
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30. COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

Author

Garcia-Valtanen, Pablo, primary, Hope, Christopher Martin, additional, Masavuli, Makutiro Ghislain, additional, Yeow, Arthur Eng Lip, additional, Balachandran, Harikrishnan, additional, Mekonnen, Zelalem Addis, additional, Al-Delfi, Zahraa, additional, Abayasingam, Arunasingam, additional, Agapiou, David, additional, Ospina Stella, Alberto, additional, Aggarwal, Anupriya, additional, Gummow, Jason, additional, Ferguson, Catherine, additional, O'Connor, Stephanie, additional, McCartney, Erin M, additional, Lynn, David J, additional, Maddern, Guy, additional, Gowans, Eric J, additional, Reddi, Benjamin AJ, additional, Shaw, David, additional, Kok-Lim, Chuan, additional, Turville, Stuart G, additional, Beard, Michael R, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Bull, Rowena A, additional, Barry, Simon C, additional, and Grubor-Bauk, Branka, additional

Published
2021
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31. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Author

Ryan, Feargal J., primary, Hope, Christopher M., additional, Masavuli, Makutiro G., additional, Lynn, Miriam A., additional, Mekonnen, Zelalem A., additional, Lip Yeow, Arthur Eng, additional, Garcia-Valtanen, Pablo, additional, Al-Delfi, Zahraa, additional, Gummow, Jason, additional, Ferguson, Catherine, additional, O’Connor, Stephanie, additional, Reddi, Benjamin AJ, additional, Shaw, David, additional, Kok-Lim, Chuan, additional, Gleadle, Jonathan M., additional, Beard, Michael R., additional, Barry, Simon C., additional, Grubor-Bauk, Branka, additional, and Lynn, David J., additional

Published
2021
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32. Long-term persistence of RBD+ memory B cells encoding neutralizing antibodies in SARS-CoV-2 infection

Author

Abayasingam, Arunasingam, Balachandran, Harikrishnan, Agapiou, David, Hammoud, Mohamed, Rodrigo, Chaturaka, Keoshkerian, Elizabeth, Li, Hui, Brasher, Nicholas A., Christ, Daniel, Rouet, Romain, Burnet, Deborah, Grubor-Bauk, Branka, Rawlinson, William, Turville, Stuart, Aggarwal, Anupriya, Stella, Alberto Ospina, Fichter, Christina, Brilot, Fabienne, Mina, Michael, Post, Jeffrey J., Hudson, Bernard, Gilroy, Nicky, Dwyer, Dominic, Sasson, Sarah C., Tea, Fiona, Pilli, Deepti, Kelleher, Anthony, Tedla, Nicodemus, Lloyd, Andrew R., Martinello, Marianne, and Bull, Rowena A.

Published
2021
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34. 'One Year Later' - SARS-CoV-2-Specific Immunity in Mild Cases of COVID-19

Author

Garcia Valtanen, Pablo, primary, Hope, Christopher M., additional, Masavuli, Makutiro G, additional, Yeow, Arthur Eng Lip, additional, Balachandran, Harikrishnan, additional, Mekonnen, Zelalem A., additional, Al-Delfi, Zahraa, additional, Abayasingam, Arunasingam, additional, Agapiou, David, additional, Gummow, Jason, additional, Ferguson, Catherine, additional, O’Connor, Stephanie, additional, McCartney, Erin M., additional, Lynn, David J, additional, Maddern, Guy, additional, Gowans, Eric J, additional, Reddi, Benjamin AJ, additional, Shaw, David, additional, Chuan, Kok-Lim, additional, Beard, Michael, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Bull, Rowena Anne, additional, Barry, Simon C., additional, and Grubor-Bauk, Branka, additional

Published
2021
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35. Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses

Author

Balachandran, Harikrishnan, primary, Phetsouphanh, Chansavath, additional, Agapiou, David, additional, Adhikari, Anurag, additional, Rodrigo, Chaturaka, additional, Hammoud, Mohamed, additional, Shrestha, Lok Bahadur, additional, Keoshkerian, Elizabeth, additional, Gupta, Money, additional, Turville, Stuart, additional, Christ, Daniel, additional, King, Cecile, additional, Sasson, Sarah, additional, Bartlett, Adam, additional, Grubor-Bauk, Branka, additional, Rawlinson, William, additional, Aggarwal, Anupriya, additional, Stella, Alberto Ospina, additional, Klemm, Vera, additional, Mina, Michael M., additional, Post, Jeffrey J., additional, Hudson, Bernard, additional, Gilroy, Nicky, additional, Konecny, Pam, additional, Ahlenstiel, Golo, additional, Dwyer, Dominic, additional, Sorrell, Tania C., additional, Kelleher, Anthony, additional, Tedla, Nicodemus, additional, Lloyd, Andrew R., additional, Martinello, Marianne, additional, and Bull, Rowena Anne, additional

Published
2021
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37. Long-term persistence of neutralizing memory B cells in SARS-CoV-2

Author

Bull, Rowena, primary, Abayasingam, Arunasingam, additional, Balachandran, Harikrishnan, additional, Agapiou, David, additional, Rodrigo, Chaturaka, additional, Keoshkerian, Elizabeth, additional, Li, Hui, additional, Brasher, Nicholas, additional, Christ, Daniel, additional, Rouet, Romain, additional, Burnett, Deborah, additional, Grubor-Bauk, Branka, additional, Rawlinson, William, additional, Turville, Stuart, additional, Aggarwal, Anupriya, additional, Brilot, Fabienne, additional, Mina, Michael, additional, Post, Jeffrey, additional, Hudson, Bernard, additional, Gilroy, Nicky, additional, Dwyer, Dominic, additional, Sasson, Sarah, additional, Tea, Fiona, additional, Pilli, Deepti, additional, Tedla, Nicodemus, additional, Lloyd, Andrew, additional, and Martinello, Marianne, additional

Published
2020
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40. Long-Term Persistence of Neutralizing Memory B Cells in SARS-CoV-2

Author

Abayasingam, Arunasingam, primary, Balachandran, Harikrishnan, additional, Agapiou, David, additional, Rodrigo, Chaturaka, additional, Keoshkerian, Elizabeth, additional, Li, Hui, additional, Brasher, Nicholas, additional, Christ, Daniel, additional, Rouet, Romain, additional, Burnett, Deborah, additional, Grubor-Bauk, Branka, additional, Rawlinson, William, additional, Turville, Stuart, additional, Aggarwal, Anupriya, additional, Brilot, Fabienne, additional, Mina, Michael, additional, Post, Jeffrey J., additional, Hudson, Bernard, additional, Gilroy, Nicky, additional, Dwyer, Dominic, additional, Sasson, Sarah, additional, Tea, Fiona, additional, Pilli, Deepti, additional, Tedla, Nicodemus, additional, Lloyd, Andrew R, additional, Martinello, Marianne, additional, Bull, Rowena Anne, additional, and Group, COSIN Study, additional

Published
2020
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41. A Hepatitis C Virus DNA Vaccine Encoding a Secreted, Oligomerized Form of Envelope Proteins Is Highly Immunogenic and Elicits Neutralizing Antibodies in Vaccinated Mice

Author

Masavuli, Makutiro Ghislain, primary, Wijesundara, Danushka K., additional, Underwood, Alexander, additional, Christiansen, Dale, additional, Earnest-Silveira, Linda, additional, Bull, Rowena, additional, Torresi, Joseph, additional, Gowans, Eric J., additional, and Grubor-Bauk, Branka, additional

Published
2019
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42. Induction of genotype cross-reactive, hepatitis C virus-specific, cellmediated immunity in DNA-vaccinated mice

Author

Wijesundara, Danushka K, Gummow, Gason, Li, Yanrui, Yu, Wenbo, Quah, Ben, Ranasinghe, Charani, Torresi, Joseph, Gowans, Eric J, Grubor-Bauk, Branka, Wijesundara, Danushka K, Gummow, Gason, Li, Yanrui, Yu, Wenbo, Quah, Ben, Ranasinghe, Charani, Torresi, Joseph, Gowans, Eric J, and Grubor-Bauk, Branka

Abstract

A universal hepatitis C virus (HCV) vaccine should elicit multiantigenic, multigenotypic responses, which are more likely to protect against challenge with the range of genotypes and subtypes circulating in the community. A vaccine cocktail and vaccines encoding consensus HCV sequences are attractive approaches to achieve this goal. Consequently, in a series of mouse vaccination studies, we compared the immunogenicity of a DNA vaccine encoding a consensus HCV nonstructural 5B (NS5B) protein to that of a cocktail of DNA plasmids encoding the genotype 1b (Gt1b) and Gt3a NS5B proteins. To complement this study, we assessed responses to a multiantigenic cocktail regimen by comparing a DNA vaccine cocktail encoding Gt1b and Gt3a NS3, NS4, and NS5B proteins to a single-genotype NS3/4/5B DNA vaccine. To thoroughly evaluate in vivo cytotoxic T lymphocyte (CTL) and T helper (Th) cell responses against Gt1b and Gt3a HCV peptide-pulsed target cells, we exploited a novel fluorescent-target array (FTA). FTA and enzyme-linked immunosorbent spot (ELISpot) analyses collectively indicated that the cocktail regimens elicited higher responses to Gt1b and Gt3a NS5B proteins than those with the consensus vaccine, while the multiantigenic DNA cocktail significantly increased the responses to NS3 and NS5B compared to those elicited by the single-genotype vaccines. Thus, a DNA cocktail vaccination regimen is more effective than a consensus vaccine or a monovalent vaccine at increasing the breadth of multigenotypic T cell responses, which has implications for the development of vaccines for communities where multiple HCV genotypes circulate.

Published
2018

50. Vaccination for pregnant women: Need to address

Author

Yu, Wenbo, Grubor-Bauk, Branka, Mullick, Ranajoy, Das, Saumitra, and Gowans, Eric J

Subjects
Counseling, medicine.medical_specialty, Immunology, Pneumococcal Vaccines, Papillomavirus Vaccines, Pregnancy, medicine, Immunology and Allergy, Humans, Hepatitis B Vaccines, reproductive and urinary physiology, LICENSED VACCINES/Commentaries, Asthma, Pharmacology, Microbiology & Cell Biology, Fetus, Obstetrics, business.industry, Vaccination, Life time, Immunization, Passive, Infant, Newborn, medicine.disease, Immunization, Influenza Vaccines, Female, business, Postpartum period
Abstract

Pregnancy is a critically important state for any women in her life time. Administration of a vaccine to a pregnant woman is not a routine event and it is generally preferred to administer vaccines either prior to conception or in the postpartum period. Currently vaccination with inactivated vaccines are recommended due to potential risk to mother and fetus with live vaccines. Multiple factors determine the administration of the vaccines for example age, life style, medical conditions (e.g., asthma, diabetes etc.), type and location of travel and status of previous vaccination. If pregnant woman is exposed to these vaccines or if pregnancy occurs soon after vaccination, the women should be counselled regarding the risks to the fetus and vaccination should not be a reason to consider termination of pregnancy. Further research in vaccination among pregnancy is warranted for the safety of the pregnant women and their newborn for a healthy living and better life.

Published
2014

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