학술논문
Off‐target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2: implications for protection against severe COVID‐19
Document Type
Report
Author
Messina, Nicole L.; Germano, Susie; Mcelroy, Rebecca; Rudraraju, Rajeev; Bonnici, Rhian; Pittet, Laure F.; Neeland, Melanie R.; Nicholson, Suellen; Subbarao, Kanta; Curtis, Nigel; Baena, Adrian Siles; Teo, Jia Wei; Lima, Guilherme Teodoro; Abreu, Carolinne; Abruzzo, Veronica; Addlem, Lynne; Agius, Sophie; Barbosa, Adelita Agripina Refosco; Alamrousi, Ahmed; Dos Santos, Ayla Alcoforado Da Silva; Al‐Hindawi, Yasmeen; Da Silveira, Samyra Almeida; Da Cruz, Lais Alves; Anderson, Jeremy; Nelly, Amenyogbe; Anthony, Christina; Pereira, Andrea Antonia Souza De Almeida Dos Reis; Almajano, Francisco Arnaiz Las Revillas; Arnold, Annabelle; Arrowsmith, Beth; Azzopardi, Kristy; Marti, Cristina Badia; Bahaduri, Twinkle; Bannister, Samantha; Barney, Sarah; Barrera, Lydia; Barriocanal, Anabel; Barros, Dayanne; Barry, Simone; Bartlett, Adam; Batista, Lilian; Muranaka, Silva; Baulman, Therese; Bealing, Morgan; Beardsley, Justin; Gutierrez, Ana Belen Martin; Bell, Jason; Benson, Saoirse; Rym, Benothman; Bennett‐Wood, Vicki; Bergant, Nikki; Barbosa, Fabiane Bianca; Bijllaardt, Wouter; Bimboese, Patricia; Andrade, Camila Bitencourt; Blake, Stephen; Blauwendraat, Kitty; Boersma, Wim; Garcia, Pilar Bohedo; Bonten, Marc; Boon, Anne; Bourke, Anna; Bowes, Kirsty; Brasil, Larissa; Brophy, Clare; Botten, Rochelle; Buchanan, Sandy; Bucholc, Jess; Burns, Alison; Burrell, Emma; Bustos, Natalia; Byrne, Bridie; Byrne, Anthony; Calbo, Esther; Montes, Jorge Calvo; Camesella, Beatriz; Campbell, John; Cangas, Atsegiñe; Carlin, John; Roque, Maria Carmen; Diogo, Roberta Carolina Pereira; Carvalho, Estela; Casas, Irma; Castro, Erika; Castro, Ramon; Catterick, Helen; Escobar, Rodrigo Cezar Dutra; Chan, Joyce; Cheah, Jo; Chern, Tee Yee; Chengodu, Thilakavathi; Ciaverella, Marianna; Clark, Sharon; Espindola, Marie‐Alix Clement; Cobbledick, Annie; Colaco, Clinton; Collopy, Simone; Comella, Patricia; Corbett, Mary; Castro, Gabriela Correa E.; Costa, Erlane; Coya, Raquel; Crawford, Nigel; Croda, Julio; Cruz, Alda; Maxwell, Curtis; Cushnahan, Jac; Czajko, Anna; Silva, Renato Da Costa; Daitiri, Bouchra; Dalcolmo, Margareth; Dalton, Karen; Dang, Thanh; Dao, Aiken; Davidson, Andrew; Dawe, Phoebe; Dawson, Diane; Costa, Miriam Jesus; De La Cruz, Karina; La Serna, Almudena; Batista, Fabiani Morais; Oliveira, Adriely; Morillo, Rocio Del Alba Rey; Desylva, Maria; Dijkstra, Helga; Dixon, Rachel; Lopez, Maria Dolores Del Toro; Dominguez, Jose; Doran, Catriona; Castellano, Angel Dominguez; Dos Santos, Glauce; Lencina, Joyce Dos Santos; Silva, Débora Dos Santos; Douglas, Mark; Dunn, Ross; Dunn, Andrew; Dunnill, Jemma; Eden, Georgina; Peta, Edler; Edmund, Harriet; Eiffler, Nat; Elborough, Hannah; Elia, Sonja; Elkington, Olivia; England, Michelle; Ayala, Wellyngthon Espindola; Esteve, Maria; Evans, Nick; Evans, Sue; Ewe, Krist; Álvarez, María Carmen Fariñ; Fahey, Kieran; Fairweather, Jill; Faustman, Denise; Silva, Erica Fernandes; Fernandez, Monique; Fidler, Galina; Filius, Pmg; Finn, Adam; Finucane, Carolyn; Firth, Stephanie; Fletcher, Emily; Flynn, Catherine; Flynn, Lorraine; Fouracre, Liam; Fowler, Sarah; Freitas, Thamires; Furtado, Ana Carolina; Oliveira, Maria Gabriela; Santos, Anna Gabriela; Gonçalves, Leandro Galdino Cavalcanti; Galletta, Laura; Gama, Larissa; Gamage, Dinusha; Ganpat, Radhika; García, Carlos; Croda, Mariana Garcia; Gardiner, Kaya; Gardiner, Evangeline; Gell, Grace; Oliveira, Aline Gerhardt; Gibbons, Michael; Gibson, Camille; Gifford, Alison; Poderos, Teresa Giménez; Ginsberg, Ann; Gisolf, Jet; Gladanac, Bojana; Glenn, Penny; Godinho, Vanessa; Dos Santos, Mayara Góes; Goikoetxea, Josune; Goldenberg, Telma; Gomes, Adriano; Marcos, Susana Gonzalez; Rico, Claudia González; Goodall, Casey; Goodchild, Louise; Gordon, Victoria; Greven, Frances; Capella, Ana Greyce; Griffith, Liddy; Guo, Christina; Campos, David Gutierrez; Cuadra, Manuel Gutierrez; Gwee, Amanda; Hall, Richard; Hall, Lydia; Hamilton, Kate; Hannan, Matthew; Harbech, Houda; Harding, Alex; Harker, Neil; Harrison, Robert; Hassing, Robert Jan; Da Rosa, Thaynara Haynara Souza; Haywood, Zaheerah; Heath, Christine; Henare, Nadine; Andrade, Paulo Henrique; Herrmann, Susan; Hill, Erin; Hilton, Sam; Huijbens, Danique; Hutton, Heidi; James, Jane; Jamieson, Tenaya; Janssen, Axel; Jardim, Bruno; Jardim, Tyane; Jarvis, Lance; Jenkins, Narelle; Jones, Jane; Jones, Jan; Jones, Karen; Jorge, Leticia; Vilegas, Maria Jose Rios; Joshi, Sri; Joyce, Rosemary; Junior, Joel; Kandasamy, Rama; Karunanayake, Anushka; Karuppasamy, Hana; Keeble, Tom; Kent, Jennifer; Kloeg, Paul; Kluytmans, Jan; Knight, Bridget; Kollmann, Tobias; Korman, Tony; Krastev, Ann; Krieg, Meredith; La, Nathan; Lacerda, Marcus; Lacoma, Alicia; Lagunday, Renier; Lalich, Debbie; Latkovic, Erin; Latorre, Irene; Meireles, Paulo Leandro Garcia; Lee, Katherine; Legge, Donna; Lemmers, Toos; Leurink, Titia; Lieschke, Katherine; Lim, Kee; Lockhart, Gemma; Bogéa, Cíntia Lopes; Dos Santos, Karla Lopes; Marques, Reyes Lopez; Lucas, Michaela; Lynn, David; Lynn, Miriam; De Freitas, Maria Luciana Silva; Norine; Macalister, Sam; Machado, Cristiane; Ramos, Matheus Machado; Machingaifa, Francesca; Maia, Ivan; Maia, Bernardo; Malley, Richard; Manning, Laurens; Manton, Sarah; Carrerero, Jose Manuel; Barriocanal, Ana Maria; Alves, Cíntia Maria Lopes; Pereira, Rosa Maria Plácido; Arruda, Bianca Maria Silva Menezes; Marins, Adriana; Markow, Angela; Marshall, Helen; Martin, Christopher; Almeida, Katya Martinez; Mather, Wayne; Mathers, Megan; Gomes, Fábio Mauricio Nogueira; Tadokoro, Mariana Mayumi; Mazarakis, Nadia; Mazurega, Kelry; Mcalister, Sonia; Mcandrews, Amy; Mcdonald, Ellie; Mcdonald, Fiona; Mcmillan, Mark; Mcmullan, Brendan; Mcphate, Nick; Mead, Lee; Meehan, Andrea; Meek, Bob; Melo, Rosangela; Mena, Guillermo; Mesquita, Daniella; Mezzetti, Isabella; Vieira, Hugo Miguel Ramos; Miller, Skye; Mitchell, Kirsten; Mitchell, Marcus; Mojeed, Jesutofunmi; Molenaar, Kitty; Molina, Gemma; Molina, Barbara; Montgomery, Lisa; Moore, Cecilia; Moore, James; Moorlag, Simone; Morawakage, Thilanka; Moss, Julie; Moyle, Will; Mulholland, Kim; Munns, Craig; Nascimento, Elizandra; Navarrette, Nicolas; Netea, Mihai; Neves, Juliana; Newman, Georgina; Ngien, Belle; Nguyen, Jill; Nguyen, Khanh; Noonan, Fran; Norton, Wendy; O’Donnell, Melissa; O’Bryan, Jess; O’Connell, Abby; Odoi, Sasha; O’Donnell, Liz; Oliveira, Roberto; Oliveira, Marilena; Oliveira, Thais; Oliveira, Ingrid; Olivier, Nadia; Olivio, Ligia; Ong, Benjamin; Ong, Jaslyn; Ong, Joanne; Onysk, Jakob; Ooi, Isabelle; Oppedisano, Frances; Orsini, Francesca; Ortika, Belinda; Otsuka, Arthur; Overton, Kristen; Owens, Rosie; Paes, Rayssa; Palasanthiran, Pamela; Jiménez, Virginia Palomo; Pandine, Girlene; Parkin, Kimberley; Hernandez, Alvaro Pascual; Paternotte, Nienke; Paterson, David; Souza, Ana Paula Conceição; Pelayo, Lisa; Pell, Casey; Pelser, Sille; Pereira, Handerson; Pereira, Gabrielle; Perez, Glady; Perez, Cristina; Porcuna, Tomás Perez; Perlen, Susan; Perrett, Kirsten; De Floy, Amandine Philippart; Pitkin, Sigrid; Pon, Rc; Calderón, Ines Portillo; Post, Jeffrey; Power, Catherine; Prado, Christiane; Prajitno, Endriaen; Prat‐Aymerich, Cristina; Preijers, Lieke; Puga, Marco; Queiroz, Evelyn; Quinn, Lynne; Rak, Ashleigh; Figueiredo, Leticia Ramires; Arellano, Encarnacion Ramirez; Ramos, Pedro; Oliveira, Karla Regina Warszawski; Ren, Jack; Reynolds, Stephanie; Rhodes, Shelley; Dos Santos, Claudinalva Ribeiro; Richards, Chris; Richmond, Peter; Richmond, Holly; Souza, Ana Rita Lopes; Rocha, Jorge; Rodrigues, Teresa; Rodrigues, Laleyska; Rodrigues, Bebeto; Fernandes, Iara Rodrigues; Rodríguez‐Baño, Jesús; Roescher, Nienke; Rogers, Sally; Rol, Anke; Romme, Jannie; Rosell, Antoni; Font, Maria Roser; Sacca, Domenic; Sallent, Sonia; Sampaio, Vanderson; Sanchez, Nuria; Sanchez, Blanca; Santos, Daniel; Santos, Tilza; Sartim, Ariandra; Sastry, Amber; Sawka, Alice; Schultz, Nikki; Seamark, Clare; Seamark, David; Septer‐Bijleveld, Engelien; Serrano, Raquel; Shann, Frank; Sharma, Ketaki; Shave, Margaret; Shen, Lisa; Sidaway‐Lee, Kate; Silva, Rafaela; Silva, Juliana; Silva, Emanuelle; Simão, Mariana; Singh, Ronita; Siqueira, Marilda; Chaves, Marciléia Soares D. Allão; Sondag, Thijs; Sooriyarachchi, Enoshini; Sousa, Antonny; Judith, Spotswood; Spry, Leena; Statton, Sarah; Steer, Andrew; Dos Santos, Dyenyffer Stéffany Leopoldina; Sterling, Katrina; Steve, Leah; Stevens, Luke; Stevens, Natalie; Stewart, Carolyn; Stiglmayer, Lisa; Stooper, Lida; Studham, Josephine; Sudbury, Eva; Suiker, Astrid; Symons, Lorrie; Taks, Esther; Tan, Niki; Meireles, Bruna Tayara Leopoldina; Riele, Menno Te; Ten Oever, Jaap; Ter Heine, Rob; Angelo, Jhenyfer Thalyta Campos; Thomson, Helen; Toh, Ryan; Trindade, Alexandre; Tripp, Harry; Tristán, Enriqueta; Troeman, Darren; Truelove, Alexandra; Tsuha, Daniel; Uffing, Marlot; Val, Fernando; Valero, Olga; Valls, Ester; Ven, Chantal; Den Heuvel, Leo; Veen, Sigrid Der; Waal, Marije Der; Leusen, Jh; Mook, Linda; Onzenoort, H; Opdorp, Marjoleine; Rijen, Miranda; Sluis, Nicolette; Vasconcelos, Adria; Vega, Noelia; Velagapudi, Sunitha; Vennells, Louise; Venton, Tamsin; Verheij, Harald; Verhoeven, P.M.; Ramos, Caroliny Veron; Da Silva, Paulo Victor Rocha; Vidal, Sandra; Vidmar, Suzanna; Vieira, Patricia; Oliveira, Matheus Vieira; Ortega, Rosario Vigo; Villanueva, Paola; Villar, Raquel; Vlahos, Amanda; Wadia, Ushma; Walker, Mary; Wall, Kate; Wallace, Rachael; Wang, Xiaofang; Waring, Justin; Warren, Ruth; Warris, Adilia; Watts, Emma; Wearing‐Smith, Michelle; Webber‐Rookes, Daniel; Wedderburn, Jamie; Wee‐Hee, Ashleigh; Wesselingh, Steve; Whale, Bethany; Williams, Phoebe; Wolters, Beatrijs; Wood, Nick; Xie, Ivy; Younes, Angela; Young, Angela; Zampieri, Felipe; Batista, Vieira; Zhou, Carmen; Zwart, Vivian
Source
Clinical & Translational Immunology. April 2022, Vol. 11 Issue 4
Subject
Language
English
Abstract
Introduction The paradigm of vaccination is the induction of antigen‐specific memory in adaptive immune cells. However, it is increasingly recognised that vaccines can have beneficial off‐target (aka non‐specific or heterologous) [...]
: Background and objectives: Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using samples from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. Methods: This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. Results: BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4[sup.+] and CD8[sup.+] T cells, and an activation of eosinophils in response to SARS‐CoV‐2. Conclusions: The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.
: Background and objectives: Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using samples from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. Methods: This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. Results: BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4[sup.+] and CD8[sup.+] T cells, and an activation of eosinophils in response to SARS‐CoV‐2. Conclusions: The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.