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1. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control studyResearch in context

Author

Avi Kenny, Janine van Duijn, One Dintwe, Jack Heptinstall, Randy Burnham, Sheetal Sawant, Lu Zhang, Dieter Mielke, Sharon Khuzwayo, Faatima Laher Omar, Sherry Stanfield-Oakley, Taylor Keyes, Brooke Dunn, Derrick Goodman, Youyi Fong, David Benkeser, Rodger Zou, John Hural, Ollivier Hyrien, Michal Juraska, Alex Luedtke, Lars van der Laan, Elena E. Giorgi, Craig Magaret, Lindsay N. Carpp, Laura Pattacini, Tom van de Kerkhof, Bette Korber, Wouter Willems, Leigh H. Fisher, Hanneke Schuitemaker, Edith Swann, James G. Kublin, Maria G. Pau, Susan Buchbinder, Frank Tomaka, Steven Nijs, Ludo Lavreys, Huub C. Gelderblom, Lawrence Corey, Kathryn Mngadi, Glenda E. Gray, Erica Borducchi, Jenny Hendriks, Kelly E. Seaton, Susan Zolla-Pazner, Dan H. Barouch, Guido Ferrari, Stephen C. De Rosa, M Juliana McElrath, Erica Andersen-Nissen, Daniel J. Stieh, Georgia D. Tomaras, Peter B. Gilbert, Jon Allagappen, Jessica Andriesen, Alison Ayres, Saman Baral, Linda-Gail Bekker, Asiphe Besethi, Caroline Borremans, Esmee Braams, Caroline Brackett, William Brumskine, Roma Chilengi, Rachel Choi, Thozama Dubula, Jaiden Seongmi Dumas, Radhika Etikala, Zelda Euler, Sarah Everett, Nigel Garrett, Huub Gelderblom, Katherine Gill, Kevin Gillespie, Dimitri Goedhart, Erik Goosmann, Shannon Grant, Ellie Hands, Barton Haynes, Bronwill Herringer, Zaheer Hoosain, Mina Hosseinipour, Portia Hunidzarira, Julia Hutter, Mubiana Inambao, Craig Innes, William Kilembe, Philippus Kotze, Sheena Kotze, Fatima Laher, Imre Laszlo, Erica Lazarus, Hua-Xin Liao, Yong Lin, Helen Lu, Judith Lucas, Mookho Malahleha, Tara McNair, Peter Meerts, Zinhle Mgaga, Mahlodi Montlha, Boitumelo Mosito, Andrew Moultrie, Sarah Mudrak, Valérie Oriol-Mathieu, Marcella Sarzotti-Kelsoe, Matson Tso Mathebula, Mitch Matoga, Rachael McClennen, Pamela Mda, Vimla Naicker, Logashvari Naidoo, Cindy-Ann Okkers, Saleha Omarjee, Hella Pasmans, Tricia Philip, Abraham Pinter, Annah Pitsi, Ornelia Ramos, April Randhawa, Sanne Roels, Shamiska Rohith, Lucy Rutten, Jerald Sadoff, Gabriela Salinas, Yvonne Salzgeber, Lorenz Scheppler, Katharine Schwedhelm, Nicolette Schuller, Angelina Sharak, Carrie Sopher, Terence Tafatatha, Simbarashe G. Takuva, Chan Tang, An Vandebosch, Edna Viegas, Valentin Voillet, Frank Wegmann, Mo Weijtens, Stephany Wilcox, Anthony Williams, Chenchen Yu, Pei-Chun Yu, Olive Yuan, and Xuehan Zhang

Subjects
Ad26.Mos4.HIV vaccine regimen, Binding antibodies, Correlates of risk, Correlates of protection, IgG3 V1V2 antibodies, Maximal signal diversity-weighted average, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

Published
2024
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2. Risk of COVID-19 after natural infection or vaccinationResearch in context

Author

Anne-Marie Rick, Matthew B. Laurens, Ying Huang, Chenchen Yu, Thomas C.S. Martin, Carina A. Rodriguez, Christina A. Rostad, Rebone M. Maboa, Lindsey R. Baden, Hana M. El Sahly, Beatriz Grinsztejn, Glenda E. Gray, Cynthia L. Gay, Peter B. Gilbert, Holly E. Janes, James G. Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M. Dunkle, Kathleen M. Neuzil, Lawrence Corey, Paul A. Goepfert, Stephen R. Walsh, Dean Follmann, Karen L. Kotloff, Atoya Adams, Eric Miller, Bruce G. Rankin, Steven Shinn, Marshall Nash, Sinikka L. Green, Colleen Jacobsen, Jayasree Krishnankutty, Sikhongi Phungwayo, Richard M. Glover, II, Stacy Slechta, Troy Holdeman, Robyn Hartvickson, Amber Grant, Terry L. Poling, Terry D. Klein, Thomas C. Klein, Tracy R. Klein, William B. Smith, Richard L. Gibson, Jennifer Winbigler, Elizabeth Parker, Priyantha N. Wijewardane, Eric Bravo, Jeffrey Thessing, Michelle Maxwell, Amanda Horn, Catherine Mary Healy, Christine Akamine, Laurence Chu, R. Michelle Chouteau, Michael J. Cotugno, George H. Bauer, Jr., Greg Hachigian, Masaru Oshita, Michael Cancilla, Kristen Kiersey, William Seger, Mohammed Antwi, Allison Green, Anthony Kim, Michael Desjardins, Jennifer A. Johnson, Amy Sherman, Judith Borger, Nafisa Saleem, Joel Solis, Martha Carmen Medina, Westly Keating, Edgar Garcia, Cynthia Bueno, Nathan Segall, Douglas S. Denham, Thomas Weiss, Ayoade Avworo, Parke Hedges, Cynthia Becher Strout, Rica Santiago, Yvonne Davis, Patty Howenstine, Alison Bondell, Kristin Marks, Tina Wang, Timothy Wilkin, Mary Vogler, Carrie Johnston, Michele P. Andrasik, Jessica G. Andriesen, Gail Broder, Niles Eaton, Huub G. Gelderblom, Rachael McClennen, Nelson Michael, Merlin Robb, Carrie Sopher, Vicki E. Miller, Fredric Santiago, Blanca Gomez, Insiya Valika, Amy Starr, Valeria D. Cantos, Sheetal Kandiah, Carlos del Rio, Nadine Rouphael, Srilatha Edupuganti, Evan J. Anderson, Andres Camacho-Gonzalez, Satoshi Kamidani, Meghan Teherani, David J. Diemert, Elissa Malkin, Marc Siegel, Afsoon Roberts, Gary Simon, Bindu Balani, Carolene Stephenson, Steven Sperber, Cristina Cicogna, Marcus J. Zervos, Paul Kilgore, Mayur Ramesh, Erica Herc, Kate Zenlea, Abram Burgher, Ann M. Milliken, Joseph D. Davis, Brendan Levy, Sandra Kelman, Matthew W. Doust, Denise Sample, Sandra Erickson, Shane G. Christensen, Christopher Matich, James Longe, John Witbeck, James T. Peterson, Alexander Clark, Gerald Kelty, Issac Pena-Renteria, Michael J. Koren, Darlene Bartilucci, Alpa Patel, Carolyn Tran, Christina Kennelly, Robert Brownlee, Jacob Coleman, Hala Webster, Carlos A. Fierro, Natalia Leistner, Amy Thompson, Celia Gonzalez, Lisa A. Jackson, Janice Suyehira, Milton Haber, Maria M. Regalado, Veronica Procasky, Alisha Lutat, Carl P. Griffin, Ripley R. Hollister, Jeremy Brown, Melody Ronk, Wayne L. Harper, Lisa Cohen, Lynn Eckert, Matthew Hong, Rambod Rouhbakhsh, Elizabeth Danford, John Johnson, Richard Calderone, Shishir K. Khetan, Oyebisi Olanrewaju, Nan Zhai, Kimberly Nieves, Allison O'Brien, Paul S. Bradley, Amanda Lilienthal, Jim Callis, Adam B. Brosz, Andrea Clement, Whitney West, Luke Friesen, Paul Cramer, Frank S. Eder, Ryan Little, Victoria Engler, Heather Rattenbury-Shaw, David J. Ensz, Allie Oplinger, Brandon J. Essink, Jay Meyer, Frederick Raiser, III, Kimberly Mueller, Keith W. Vrbicky, Charles Harper, Chelsie Nutsch, Wendell Lewis, III, Cathy Laflan, Jordan L. Whatley, Nicole Harrell, Amie Shannon, Crystal Rowell, Christopher Dedon, Mamodikoe Makhene, Gregory M. Gottschlich, Kate Harden, Melissa Gottschlich, Mary Smith, Richard Powell, Murray A. Kimmel, Simmy Pinto, Timothy P. Vachris, Mark Hutchens, Stephen Daniels, Margaret Wells, Mimi Van Der Leden, Peta-Gay Jackson-Booth, Mira Baron, Pamela Kane, Shannen Seversen, Mara Kryvicky, Julia Lord, Jamshid Saleh, Matthew Miles, Rafael Lupercio, John W. McGettigan, Jr., Walter Patton, Riemke Brakema, Karin Choquette, Jonlyn McGettigan, Judith L. Kirstein, Marcia Bernard, Mary Beth Manning, Joan Rothenberg, Toby Briskin, Denise Roadman, Sharita Tedder-Edwards, Howard I. Schwartz, Surisday Mederos, Shobha Swaminathan, Amesika Nyaku, Tilly Varughese, Michelle DallaPiazza, Sharon E. Frey, Irene Graham, Getahun Abate, Daniel Hoft, Leland N. Allen, III, Leslie A. Edwards, William S. Davis, Jr., Jessica M. Mena, Mark E. Kutner, Jorge Caso, Maria Hernandez Moran, Marianela Carvajal, Janet Mendez, Larkin T. Wadsworth, III, Michael R. Adams, Leslie Iverson, Joseph L. Newberg, Laura Pearlman, Paul J. Nugent, Michele D. Reynolds, Jennifer Bashour, Robert Schmidt, Neil P. Sheth, Kenneth Steil, Ramy J. Toma, William Kirby, Pink Folmar, Samantha Williams, Paul Pickrell, Stefanie Mott, Carol Ann Linebarger, Hussain Malbari, David Pampe, Veronica G. Fragoso, Lisa Holloway, Cecilia McKeown-Bragas, Teresa Becker, Barton G. Williams, William H. Jones, Jesse L. Clark, Steven Shoptaw, Michele Vertucci, Will Hernandez, Stephen A. Spector, Amaran Moodley, Jill Blumenthal, Lisa Stangl, Karen Deutsch, Kathleen M. Mullane, David Pitrak, Cheryl Nuss, Judy Pi, Carl Fichtenbaum, Margaret Powers-Fletcher, Michelle Saemann, Sharon Kohrs, Thomas B. Campbell, Andrew Lauria, Jose C. Mancilla, Hillary Dunlevy, Richard M. Novak, Andrea Wendrow, Scott Borgetti, Ben Ladner, Lisa Chrisley, Cheryl Young, Susanne Doblecki-Lewis, Maria L. Alcaide, Jose Gonzales-Zamora, Stephen Morris, David Wohl, Joseph Eron, Jr., Ian Frank, Debora Dunbar, David Metzger, Florence Momplaisir, Judith Martin, Alejandro Hoberman, Timothy Shope, Gysella Muniz, Richard Rupp, Amber Stanford, Megan Berman, Laura Porterfield, Michael Lewis, Elham Ghadishah, Joseph Yusin, Mai Pham, Clarence B. Creech, II, Shannon Walker, Stephanie Rolsma, Robert Samuels, Isaac Thomsen, Spyros A. Kalams, Greg Wilson, Gregg H. Lucksinger, Kevin Parks, Ryan Israelsen, Jaleh Ostovar, Kary Kelly, Jeffrey S. Overcash, Hanh Chu, Kia Lee, Luis I. De La Cruz, Steve Clemons, Elizabeth Everette, Suzanna Studdard, Gowdhami Mohan, Stefanie Tyson, Alyssa-Kay Peay, Danyel Johnson, Gregory J. Feldman, May-Yin Suen, Jacqueline Muenzner, Joseph Boscia, Farhan Siddiqui, John Sanders, James Peacock, Julio Nasim, Michael L. Levin, Julie Hussey, Marcy Kulic, Mark M. McKenzie, Teresa Deese, Erica Osmundsen, Christy Sweet, Valentine M. Ebuh, Elwaleed Elnagar, Georgette Ebuh, Genevieve Iwuala, Laurie J. Han-Conrad, Todd Simmons, Denis Tarakjian, Jeremy Ackermann, Mark S. Adams, José O. Alemán, Mohamed S. Al-Ibrahim, David R. Andes, Jeb Andrews, Roberto C. Arduino, Martín Bäcker, Diana Badillo, Emma Bainbridge, Teresa A. Batteiger, Jose A. Bazan, Roger J. Bedimo, Jorge A. Benitez, Annette R. Bennett, David I. Bernstein, Kristin Bialobok, Rebecca Boas, Judith Brady, Cynthia Brown, Catherine A. Bunce, Robert S. Call, Wesley Campbell, Ellie Carmody, Christopher Carpenter, Steven E. Carsons, Marvin Castellon, Mario Castro, Hannah Catan, Jennifer Chang, Mouna G. Chebib, Corey M. Chen, Margaret Cheng, Brian D.W. Chow, Annie Ciambruschini, Joseph P. Connor, James H. Conway, Maureen Cooney, Marcel Curlin, Claudia De La Matta Rodriguez, Jon F. Dedon, Emily Degan, Michelle Dickey, Craig Dietz, Jennifer L. Dong, Brenda Dorcely, Michael P. Dube, Carmel B. Dyer, Benjamin Eckhardt, Edward Ellerbeck, Evan C. Ewers, Amy Falk, Brittany Feijoo, Uriel R. Felsen, Tom Fiel, David Fitz-Patrick, Charles M. Fogarty, Stacy Ford, Lina M. Forero, Elizabeth Formentini, Doris Franco-Vitteri, Robert W. Frenck, Jr., Elie Gharib, Suzanne Gharib, Rola G. Rucker, James N. Goldenberg, Luis H. González, Brett Gray, Rusty Greene, Robert M. Grossberg, Juan V. Guanira-Carranza, Alfredo Gilberto Guerreros Benavides, Clint C. Guillory, Shauna H. Gunaratne, David Halpert, Holli Hamilton, William R. Hartman, Sheryl L. Henderson, Ramin Herati, Laura Hernandez Guarin, Robin Hilder, Ken Ho, Leila Hojat, Sybil G. Hosek, Jeffrey M. Jacobson, Melanie Jay, Diane H. Johnson, Kathleen S. Jones, Edward C. Jones-López, Jessica E. Justman, Scott Kahney, Lois Katz, Melinda Katz, Daniel Kaul, Michael C. Keefer, Ashley Kennedy, Jennifer Knishinsky, Laura Kogelman, Susan L. Koletar, Angelica Kottkamp, Maryrose Laguio-Vila, Raphael J. Landovitz, Jessica L. Lee, Albert Liu, Eneyda Giuvanela Llerena Zegarra, Anna S. Lok, James Lovell, Ronald Lubelchek, John Lucaj, Gary Luckasen, Annie Luetkemeyer, Njira Lucia Lugogo, Janine Maenza, Carlos Malvestutto, Monica Mauri, Ryan C. Maves, Kenneth H. Mayer, Michael J. McCartney, Margaret E. McCort, M. Juliana McElrath, Meredith McNairy, Fernando L. Merino, Eric A. Meyerowitz, Carol L. Mitchell, Cynthia L. Monaco, Sauda Muhammad, Sigridh Muñoz-Gómez, Sonal Munsiff, Paul Nee, Nicole L. Nollen, Asif Noor, Claudio Nuñez Lagos, Jason F. Okulicz, Patrick A. Oliver, Jessica Ortega, Steven Palmer, Lalitha Parameswaran, Purvi Parikh, Susan Parker, Reza Parungao, Juana R. Pavie, Rebecca P. Madan, Henry Peralta, Jennifer Petts, Kristen K. Pierce, E. Javier Pretell Alva, Lawrence J. Purpura, Vanessa Raabe, Sergio E. Recuenco, Tamara Richards, Sharon A. Riddler, Barbara Rizzardi, Rachel Rokser, Charlotte-Paige Rolle, Adam Rosen, Jeffrey Rosen, Lena R. Freese, María E. Santolaya, Linda M. Schipani, Adam Schwartz, Tiffany Schwasinger-Schmidt, Hyman Scott, Beverly E. Sha, Shivanjali Shankaran, Adrienne E. Shapiro, Stephan C. Sharp, Bo Shopsin, Matthew D. Sims, Stephanie Skipper, Derek M. Smith, Michael J. Smith, M. Mahdee Sobhanie, Brit Sovic, Stephanie Sterling, Robert Striker, Karla Beatriz Tafur Bances, Kawsar R. Talaat, Edward M. Tavel, Jr., Hong V. Tieu, Christian Tomaszewski, Ryan Tomlinson, Juan P. Torres, Julian A. Torres, John J. Treanor, Sade Tukuru, Robert J. Ulrich, Gregory C. Utz, Veronica Viar, Roberto A. Viau Colindres, Edward E. Walsh, Mary C. Walsh, Emmanuel B. Walter, Jessica L. Weidler, Yi H. Wu, Kinara S. Yang, Juan Luis Yrivarren Giorza, Arthur L. Zemanek, Kevin Zhang, Barry S. Zingman, Richard Gorman, Carmen A. Paez, Edith Swann, Simbarashe G. Takuva, Alex Greninger, Pavitra Roychoudhury, Robert W. Coombs, Keith R. Jerome, Flora Castellino, Xiaomi Tong, Corrina Pavetto, Teletha Gipson, Tina Tong, Marina Lee, James Zhou, Michael Fay, Kelly McQuarrie, Chimeremma Nnadi, Obiageli Sogbetun, Nina Ahmad, Ian De Proost, Cyrus Hoseyni, Paul Coplan, Najat Khan, Peter Ronco, Dawn Furey, Jodi Meck, Johan Vingerhoets, Boerries Brandenburg, Jerome Custers, Jenny Hendriks, Jarek Juraszek, Anne Marit de Groot, Griet Van Roey, Dirk Heerwegh, Ilse Van Dromme, Jorge F. Méndez Galván, Monica B. Carrascal, Adriana Sordo Duran, Laura Ruy Sanchez Guerrero, Martha Cecilia Gómora Madrid, Alejandro Quintín Barrat Hernández, Sharzhaad Molina Guizar, Denisse Alejandra González Estrada, Silvano Omar Martínez Pérez, Zindy Yazmín Zárate Hinojosa, Guillermo Miguel Ruiz-Palacios, Aurelio Cruz-Valdez, Janeth Pacheco-Flores, Anyela Lara, Secia Díaz-Miralrio, María José Reyes Fentanes, Jocelyn Zuleica Olmos Vega, Daniela Pineda Méndez, Karina Cano Martínez, Winniberg Stephany Alvarez León, Vida Veronica Ruiz Herrera, Eduardo Gabriel Vázquez Saldaña, Laura Julia Camacho Choza, Karen Sofia Vega Orozco, Sandra Janeth Ortega Domínguez, Jorge A. Chacón, Juan J. Rivera, Erika A. Cutz, Maricruz E. Ortegón, María I. Rivera, David Browder, Cortney Burch, Terri Moye, Paul Bondy, Lesley Browder, Rickey D. Manning, James W. Hurst, Rodney E. Sturgeon, Paul H. Wakefield, John A. Kirby, James Andersen, Szheckera Fearon, Rosa Negron, Amy Medina, John M. Hill, Vivek Rajasekhar, Hayes Williams, LaShondra Cade, Rhodna Fouts, Connie Moya, Corey G. Anderson, Naomi Devine, James Ramsey, Ashley Perez, David Tatelbaum, Michael Jacobs, Kathleen Menasche, Vincent Mirkil, Peter J. Winkle, Amina Z. Haggag, Michelle Haynes, Marysol Villegas, Sabina Raja, Robert Riesenberg, Stanford Plavin, Mark Lerman, Leana Woodside, Maria Johnson, C. Mary Healy, Jennifer A. Whitaker, Wendy A. Keitel, Robert L. Atmar, Gary Horwith, Robin Mason, Lisa Johnson, Tambra Dora, Deborah Murray, Logan Ledbetter, Beverly Ewing, Kathryn E. Stephenson, Chen S. Tan, Rebecca Zash, Jessica L. Ansel, Kate Jaegle, Caitlin J. Guiney, Jeffrey A. Henderson, Marcia O'Leary, Kendra Enright, Jill Kessler, Pete Ducheneaux, Asha Inniss, Donald M. Brandon, William B. Davis, Daniel T. Lawler, Yaa D. Oppong, Ryan P. Starr, Scott N. Syndergaard, Rozeli Shelly, Mashrur Islam Majumder, Danny Sugimoto, Jeffrey Dugas, Sr., Dolores Rijos, Sandra Shelton, Stephan Hong, Howard Schwartz, Nelia Sanchez-Crespo, Jennifer Schwartz, Terry Piedra, Barbara Corral, Carmen Medina, Michael E. Dever, Mitul Shah, Michael Delgado, Tameika Scott, Lisa S. Usdan, Lora J. McGill, Valerie K. Arnold, Carolyn Scatamacchia, Codi M. Anthony, Rajan Merchant, Anelgine C. Yoon, Janet Hill, Lucy Ng-Price, Teri Thompson-Seim, Ronald Ackerman, Jamie Ackerman, Florida Aristy, Nzeera Ketter, Jon Finley, Mildred Stull, Monica Murray, Zainab Rizvi, Sonia Guerrero, Yogesh K. Paliwal, Amit Paliwal, Sarah Gordon, Bryan Gordon, Cynthia Montano-Pereira, Christopher Galloway, Candice Montros, Lily Aleman, Samira Shairi, Wesley Van Ever, George H. Freeman, Esther L. Harmon, Marshall A. Cross, Kacie Sales, Catherine Q. Gular, Matthew Hepburn, Nathan Alderson, Shana Harshell, Siham Mahgoub, Celia Maxwell, Thomas Mellman, Karl M. Thompson, Glenn Wortman, Jeff Kingsley, April Pixler, LaKondria Curry, Sarah Afework, Austin Swanson, Jeffry Jacqmein, Maggie Bowers, Dawn Robison, Victoria Mosteller, Janet Garvey, Mary Easley, Rebecca J. Kurnat, Raymond Cornelison, Shanda Gower, William Schnitz, Destiny S. Heinzig-Cartwright, Derek Lewis, Fred E. Newton, Aeiress Duhart, Breanz Watkins, Brandy Ball, Jill York, Shelby Pickle, David B. Musante, William P. Silver, Linda R. Belhorn, Nicholas A. Viens, David Dellaero, Priti Patel, Kendra Lisec, Beth Safirstein, Luz Zapata, Lazaro Gonzalez, Evelyn Quevedo, Farah Irani, Joseph Grillo, Amy Potts, Julie White, Patrick Flume, Gary Headden, Brandie Taylor, Ashley Warden, Amy Chamberlain, Robert Jeanfreau, Susan Jeanfreau, Paul G. Matherne, Amy Caldwell, Jessica Stahl, Mandy Vowell, Lauren Newhouse, Vladimir Berthaud, Zudi-Mwak Takizala, Genevieve Beninati, Kimberly Snell, Sherrie Baker, James Walker, Tavane Harrison, Meagan Miller, Janet Otto, Roni Gray, Christine Wilson, Tiffany Nemecek, Hannah Harrington, Sally Eppenbach, Wendell Lewis, Tana Bourgeois, Lyndsea Folsom, Gregory Holt, Mehdi Mirsaeidi, Rafael Calderon, Paola Lichtenberger, Jalima Quintero, Becky Martinez, Lilly Immergluck, Erica Johnson, Austin Chan, Norberto Fas, LaTeshia Thomas-Seaton, Saadia Khizer, Jonathan Staben, Tatiana Beresnev, Maryam Jahromi, Mary A. Marovich, Julia Hutter, Martha Nason, Julie Ledgerwood, John Mascola, Mark Leibowitz, Fernanda Morales, Mike Delgado, Rosario Sanchez, Norma Vega, Germán Áñez, Gary Albert, Erin Coston, Chinar Desai, Haoua Dunbar, Mark Eickhoff, Jenina Garcia, Margaret Kautz, Angela Lee, Maggie Lewis, Alice McGarry, Irene McKnight, Joy Nelson, Patrick Newingham, Patty Price-Abbott, Patty Reed, Diana Vegas, Bethanie Wilkinson, Katherine Smith, Wayne Woo, Iksung Cho, Gregory M. Glenn, Filip Dubovsky, David L. Fried, Lynne A. Haughey, Ariana C. Stanton, Lisa Stevens Rameaka, David Rosenberg, Lee Tomatsu, Viviana Gonzalez, Millie Manalo, Bernard Grunstra, Donald Quinn, Phillip Claybrook, Shelby Olds, Amy Dye, Kevin D. Cannon, Mesha M. Chadwick, Bailey Jordan, Morgan Hussey, Hannah Nevarez, Colleen F. Kelley, Michael Chung, Caitlin Moran, Paulina Rebolledo, Christina Bacher, Elizabeth Barranco-Santana, Jessica Rodriguez, Rafael Mendoza, Karen Ruperto, Odette Olivieri, Enrique Ocaña, Paul E. Wylie, Renea Henderson, Natasa Jenson, Fan Yang, Amy Kelley, Kenneth Finkelstein, David Beckmann, Tanya Hutchins, Sebastian Garcia Escallon, Kristen Johnson, Teresa S. Sligh, Parul Desai, Vincent Huynh, Carlos Lopez, Erika Mendoza, Jeffrey Adelglass, Jerome G. Naifeh, Kristine J. Kucera, Waseem Chughtai, Shireen H. Jaffer, Matthew G. Davis, Jennifer Foley, Michelle L. Burgett, Tammi L. Shlotzhauer, Sarah M. Ingalsbe-Geno, Daniel Duncanson, Kelly Kush, Lori Nesbitt, Cora Sonnier, Jennifer McCarter, Michael B. Butcher, James Fry, Donna Percy, Karen Freudemann, Bruce C. Gebhardt, Padma N. Mangu, Debra B. Schroeck, Rajesh K. Davit, Gayle D. Hennekes, Benjamin J. Luft, Melissa Carr, Sharon Nachman, Alison Pellecchia, Candace Smith, Bruno Valenti, Maria I. Bermudez, Noris Peraita, Ernesto Delgado, Alicia Arrazcaeta, Natalie Ramirez, Carmen Amador, Horacio Marafioti, Lyly Dang, Lauren Clement, Jennifer Berry, Mohammed Allaw, Georgettea Geuss, Chelsea Miles, Zachary Bittner, Melody Werne, Cornell Calinescu, Shannon Rodman, Joshua Rindt, Erin Cooksey, Kristina Harrison, Deanna Cooper, Manisha Horton, Amanda Philyaw, William Jennings, Hilario Alvarado, Michele Baka, Malina Regalado, Linda Murray, Sherif Naguib, Justin Singletary, Sha-Wanda Richmond, Sarah Omodele, Emily Oppenheim, Reuben Martinez, Victoria Andriulis, Leonard Singer, Jeanne Blevins, Meagan Thomas, Christine Hull, Isabel Pereira, Gina Rivero, Tracy Okonya, Frances Downing, Paulina Miller, Margaret Rhee, Katherine Stapleton, Jeffrey Klein, Rosamond Hong, Suzanne Swan, Tami Wahlin, Elizabeth Bennett, Amy Salzl, Sharine Phan, Jewel J. White, Amanda Occhino, Ruth Paiano, Morgan McLaughlin, Elisa Swieboda, Veronica Garcia-Fragoso, Maria G. Becerra, Toni White, Christine B. Turley, Andrew McWilliams, Tiffany Esinhart, Natasha Montoya, Shamika Huskey, Leena Paul, Karen Tashima, Jennie Johnson, Marguerite Neill, Martha Sanchez, Natasha Rybak, Maria Mileno, Stuart H. Cohen, Monica Ruiz, Dean M. Boswell, Elizabeth E. Robison, Trina L. Reynolds, Sonja Neumeister, Carmen D. Zorrilla, Juana Rivera, Jessica Ibarra, Iris García, Dianca Sierra, Wanda Ramon, Suzanne Fiorillo, Rebecca Pitotti, Victoria R. Anderson, Jose Castillo Mancilla, Nga Le, Patricia L. Winokur, Dilek Ince, Theresa Hegmann, Jeffrey Meier, Jack Stapleton, Laura Stulken, Monica McArthur, Andrea Berry, Milagritos Tapia, Elizabeth Hammershaimb, Toni Robinson, Rosa MacBryde, Susan Kline, Joanne L. Billings, Winston Cavert, Les B. Forgosh, Timothy W. Schacker, Tyler D. Bold, Dima Dandachi, Taylor Nelson, Andres Bran, Grant Geiger, S. Hasan Naqvi, Diana F. Florescu, Richard Starlin, David Kline, Andrea Zimmer, Anum Abbas, Natasha Wilson, Joseph J. Eron, Michael Sciaudone, A. Lina Rosengren, John S. Kizer, Sarah E. Rutstein, Elizabeth Bruce, Claudia Espinosa, Lisa J. Sanders, Kami Kim, Denise Casey, Barbara S. Taylor, Thomas Patterson, Ruth S. Pinilla, Delia Bullock, Philip Ponce, Jan Patterson, R. Scott McClelland, Dakotah C. Lane, Anna Wald, Frank James, Elizabeth Duke, Kirsten Hauge, Jessica Heimonen, Erin A. Goecker, Youyi Fong, Carol Kauffman, Kathleen Linder, Kimberly Nofz, Andrew McConnell, Robert J. Buynak, Angella Webb, Taryn Petty, Stephanie Andree, Erica Sanchez, Nolan Mackey, Clarisse Baudelaire, Sarah Dzigiel, Adrienna Marquez, Kim Quillin, Michelle King, Vanessa Abad, Jennifer Knowles, Michael Waters, Karla Zepeda, Jordan Coslet, Dalia Tovar, Marian E. Shaw, Mark A. Turner, Cory J. Huffine, Esther S. Huffine, Julie A. Ake, Elizabeth Secord, Eric McGrath, Phillip Levy, Brittany Stewart, Charnell Cromer, Ayanna Walters, Grant Ellsworth, Caroline Greene, Sarah Galloway, Shashi Kapadia, Elliot DeHaan, Clint Wilson, Jason Milligan, Danielle Raley, Joseph Bocchini, Bruce McClenathan, Mary Hussain, Evelyn Lomasney, Evelyn Hall, Sherry Lamberth, Christy Schmeck, Vickie Leathers, Deborah A. Theodore, Angela R. Branche, Daniel S. Graciaa, Timothy J. Hatlen, Jacqueline Miller, Jerald Sadoff, Ann R. Falsey, and Magdalena E. Sobieszczyk

Subjects
COVID-19, Natural infection, Hybrid immunity, Vaccination, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Published
2023
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3. Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial

Author

Youyi Fong, Yunda Huang, David Benkeser, Lindsay N. Carpp, Germán Áñez, Wayne Woo, Alice McGarry, Lisa M. Dunkle, Iksung Cho, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Christos J. Petropoulos, Andrew Leith, Deanne Haugaard, Bill Webb, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, April K. Randhawa, Michele P. Andrasik, James G. Kublin, Julia Hutter, Maryam Keshtkar-Jahromi, Tatiana H. Beresnev, Lawrence Corey, Kathleen M. Neuzil, Dean Follmann, Julie A. Ake, Cynthia L. Gay, Karen L. Kotloff, Richard A. Koup, Ruben O. Donis, Peter B. Gilbert, Immune Assays Team, Coronavirus Vaccine Prevention Network (CoVPN)/2019nCoV-301 Principal Investigators and Study Team, and United States Government (USG)/CoVPN Biostatistics Team

Subjects
Science
Abstract

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

Published
2023
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4. Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults

Author

Kristen W. Cohen, Andrew Fiore-Gartland, Stephen R. Walsh, Karina Yusim, Nicole Frahm, Marnie L. Elizaga, Janine Maenza, Hyman Scott, Kenneth H. Mayer, Paul A. Goepfert, Srilatha Edupuganti, Giuseppe Pantaleo, Julia Hutter, Daryl E. Morris, Stephen C. De Rosa, Daniel E. Geraghty, Merlin L. Robb, Nelson L. Michael, Will Fischer, Elena E. Giorgi, Harman Malhi, Michael N. Pensiero, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Peter B. Gilbert, M. Juliana McElrath, Barton F. Haynes, Bette T. Korber, Lindsey R. Baden, and the NIAID HVTN 106 Study Group

Subjects
AIDS/HIV, Vaccines, Medicine
Abstract

BACKGROUND Mosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODS This double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara–vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTS Env-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2–4.2) for mosaic recipients, 1.6 (95% CI, 0.82–2.6) for CON-S recipients, and 1.1 (95% CI, 0.62–1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSION Priming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATION ClinicalTrials.gov NCT02296541.FUNDING US NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282.

Published
2023
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5. Publisher Correction: Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial

Author

Youyi Fong, Yunda Huang, David Benkeser, Lindsay N. Carpp, Germán Áñez, Wayne Woo, Alice McGarry, Lisa M. Dunkle, Iksung Cho, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Christos J. Petropoulos, Andrew Leith, Deanne Haugaard, Bill Webb, Yiwen Lu, Chenchen Yu, Bhavesh Borate, Lars W. P. van der Laan, Nima S. Hejazi, April K. Randhawa, Michele P. Andrasik, James G. Kublin, Julia Hutter, Maryam Keshtkar-Jahromi, Tatiana H. Beresnev, Lawrence Corey, Kathleen M. Neuzil, Dean Follmann, Julie A. Ake, Cynthia L. Gay, Karen L. Kotloff, Richard A. Koup, Ruben O. Donis, Peter B. Gilbert, Immune Assays Team, Coronavirus Vaccine Prevention Network (CoVPN)/2019nCoV-301 Principal Investigators and Study Team, and United States Government (USG)/CoVPN Biostatistics Team

Subjects
Science
Published
2023
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6. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.

Author

Zoe Moodie, Stephen R Walsh, Fatima Laher, Lucas Maganga, Michael E Herce, Sarita Naidoo, Mina C Hosseinipour, Craig Innes, Linda-Gail Bekker, Nicole Grunenberg, Philipp Mann, Chenchen Yu, Allan C deCamp, Maurine D Miner, Nicole L Yates, Jack Heptinstall, Nonhlanhla N Mkhize, One Dintwe, Nicole Frahm, Kristen W Cohen, Mary Allen, Julia Hutter, Ralf Wagner, Giuseppe Pantaleo, M Juliana McElrath, Georgia D Tomaras, Lynn Morris, David C Montefiori, Erica Andersen-Nissen, Glenda E Gray, Peter B Gilbert, James G Kublin, and NIAID HVTN 100 and HVTN 111 trial teams

Subjects
Medicine
Abstract

BackgroundDNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle.Methods and findingsThe primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p < 0.001) and B.CaseA V1V2 (GM 2314.0 versus 744.6, ratio = 3.11, 95% CI 1.51-6.38, p = 0.002). nAb response rates were >98% in both trials, with significantly higher 50% inhibitory dilution (ID50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects.ConclusionsIn this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy.

Published
2020
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7. A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa

Author

Linda-Gail Bekker, One Dintwe, Andrew Fiore-Gartland, Keren Middelkoop, Julia Hutter, Anthony Williams, April K. Randhawa, Morten Ruhwald, Ingrid Kromann, Peter L. Andersen, Carlos A. DiazGranados, Kathryn T. Rutkowski, Dereck Tait, Maurine D. Miner, Erica Andersen-Nissen, Stephen C. De Rosa, Kelly E. Seaton, Georgia D. Tomaras, M. Juliana McElrath, Ann Ginsberg, and James G. Kublin

Subjects
Medicine (General), R5-920
Abstract

Background: Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials. Methods: Two doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2–8 × 105 CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207). Findings: In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group. Interpretation: BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials. Funding: NIAID and Aeras. Keywords: Mycobacterium tuberculosis, H4:IC31, H56:IC31, BCG

Published
2020
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8. Benefits of risk‐adapted and mould‐specific antifungal prophylaxis in childhood leukaemia

Author

Cornelia Lass-Flörl, Christina Salvador, Gabriele Kropshofer, Julia Hutter, Andreas Meryk, Josef Fritz, and Roman Crazzolara

Subjects
Male, Antifungal, medicine.medical_specialty, Vincristine, medicine.drug_class, Antifungal drug, invasive fungal infection, liposomal amphotericin‐B, 03 medical and health sciences, 0302 clinical medicine, childhood leukaemia, Risk Factors, Amphotericin B, Internal medicine, cancer, Aspergillosis, Humans, Medicine, Child, Fluconazole, Retrospective Studies, Leukemia, business.industry, Cancer, Hematology, medicine.disease, Childhood leukaemia, Aspergillus, Tolerability, Paediatric, Child, Preschool, 030220 oncology & carcinogenesis, Female, Liposomal amphotericin, prophylaxis, business, Research Paper, 030215 immunology, medicine.drug
Abstract

Summary Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single‐centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin‐B (L‐AMB) and restricted to high‐risk patients only. Vincristine‐induced neurotoxicity was significantly reduced under L‐AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene‐treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L‐AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk‐adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.

Published
2020
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9. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

Author

David L. Fried, Wayne Woo, Julie A Ake, Iksung Cho, Alejandro Q. Barrat Hernandez, Scott McClelland, Jeffrey A. Henderson, Wayne L. Harper, Lawrence Corey, Monica A. McArthur, Veronica Garcia-Fragoso, Mark McKenzie, Dakotah C. Lane, Jeffrey K. Kingsley, Guillermo M. Ruiz-Palacios, Robert Jeanfreau, Lisa M. Dunkle, Katherine Smith, Robert W. Coombs, Daniel M. Duncanson, Alexander L. Greninger, Diana F. Florescu, Karen L. Kotloff, Robert A. Riesenberg, Filip Dubovsky, Julia Hutter, David B. Musante, Kathleen M. Neuzil, Gregory M. Glenn, Beth E. Safirstein, Jeffrey M. Adelglass, and Germán Añez

Subjects
medicine.medical_specialty, education.field_of_study, Allergy, Coronavirus disease 2019 (COVID-19), business.industry, Population, Vaccine efficacy, Placebo, medicine.disease, Confidence interval, Vaccination, Internal medicine, Clinical endpoint, Medicine, business, education
Abstract

BACKGROUNDVaccination using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antigen has been effective in the prevention of coronavirus disease 2019 (Covid-19). NVX-CoV2373 is an adjuvanted, recombinant S protein nanoparticle vaccine that demonstrated clinical efficacy for prevention of Covid-19 in phase 2b/3 trials in the United Kingdom and South Africa.METHODSThis phase 3, randomized, observer-blinded, placebo-controlled trial evaluated the efficacy and safety of NVX-CoV2373 in adults ≥18 years of age in the United States and Mexico during the first quarter of 2021. Participants were randomized in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary end point was vaccine efficacy (VE) against reverse transcriptase-polymerase chain reaction-confirmed Covid-19 in SARS-CoV-2-naïve participants ≥7 days after the second dose administration.RESULTSOf the 29,949 participants randomized between December 27, 2020, and February 18, 2021, 29,582 (median age: 47 years, 12.6% ≥65 years) received ≥1 dose: 19,714 received vaccine and 9868 placebo. In the per-protocol population, there were 77 Covid-19 cases; 14 among vaccine and 63 among placebo recipients (VE: 90.4%, 95% confidence interval [CI] 82.9 to 94.6, PCONCLUSIONSNVX-CoV2373 was well tolerated and demonstrated a high overall VE (>90%) for prevention of Covid-19, with most cases due to variant strains.(Funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; PREVENT-19 ClinicalTrials.gov number, NCT04611802.)

Published
2021
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10. A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa

Author

Anthony Williams, Georgia D. Tomaras, Andrew Fiore-Gartland, One B. Dintwe, Kathryn Tucker Rutkowski, Aeras A Protocol Team, Peter Andersen, Keren Middelkoop, Hvtn, Kelly E. Seaton, M. Juliana McElrath, Linda-Gail Bekker, Erica Andersen-Nissen, James G. Kublin, Ann M. Ginsberg, Dereck Tait, Stephen C. De Rosa, Ingrid Kromann, Julia Hutter, Carlos A. DiazGranados, April K. Randhawa, Morten Ruhwald, and Maurine D. Miner

Subjects
Research paper, Tuberculosis, 01 natural sciences, QuantiFERON, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Medicine, BCG, 030212 general & internal medicine, H56:IC31, 0101 mathematics, lcsh:R5-920, biology, business.industry, Immunogenicity, 010102 general mathematics, General Medicine, Vaccine efficacy, medicine.disease, biology.organism_classification, Vaccination, Immunology, biology.protein, Antibody, business, lcsh:Medicine (General), H4:IC31
Abstract

Background: Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials. Methods: Two doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2–8 × 105 CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207). Findings: In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group. Interpretation: BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials. Funding: NIAID and Aeras. Keywords: Mycobacterium tuberculosis, H4:IC31, H56:IC31, BCG

Published
2020

11. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials

Author

Allan C. deCamp, Mary Allen, James G. Kublin, M. Juliana McElrath, Mina C. Hosseinipour, Craig Innes, Zoe Moodie, Giuseppe Pantaleo, Jack Heptinstall, Chenchen Yu, Nonhlanhla N. Mkhize, Nicole Frahm, Peter B. Gilbert, Erica Andersen-Nissen, Maurine D. Miner, Linda-Gail Bekker, Fatima Laher, Sarita Naidoo, Glenda Gray, Kristen W. Cohen, Julia Hutter, Hvtn trial teams, Philipp Mann, Lucas Maganga, David C. Montefiori, Lynn Morris, Ralf Wagner, One Dintwe, Georgia D. Tomaras, Nicole L. Yates, Nicole Grunenberg, Stephen R. Walsh, and Michael E Herce

Subjects
Male, HIV Antigens, Physiology, Molecular biology, medicine.medical_treatment, MF59, Antibody Response, HIV Infections, 030204 cardiovascular system & hematology, HIV Antibodies, Gastroenterology, Biochemistry, White Blood Cells, 0302 clinical medicine, Animal Cells, Immune Physiology, Medicine and Health Sciences, 030212 general & internal medicine, HIV vaccine, Immune Response, AIDS Vaccines, Vaccines, Immune System Proteins, T Cells, Immunogenicity, Vaccination, General Medicine, Infectious Diseases, Medicine, Female, Cellular Types, Adjuvant, Plasmids, Research Article, Adult, medicine.medical_specialty, Infectious Disease Control, Immune Cells, Genetic Vectors, Immunology, DNA construction, Microbiology, Antibodies, 03 medical and health sciences, Young Adult, Antigen, Double-Blind Method, Internal medicine, Virology, medicine, Humans, Antigens, Blood Cells, business.industry, Viral vaccines, HIV vaccines, Biology and Life Sciences, Proteins, DNA, Cell Biology, Antibodies, Neutralizing, Research and analysis methods, Regimen, Molecular biology techniques, Antibody Formation, Plasmid Construction, HIV-1, business
Abstract

Background DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle. Methods and findings The primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%–32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42–3.92, p < 0.001) and B.CaseA V1V2 (GM 2314.0 versus 744.6, ratio = 3.11, 95% CI 1.51–6.38, p = 0.002). nAb response rates were >98% in both trials, with significantly higher 50% inhibitory dilution (ID50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67–2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48–2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%–56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%–63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%–82.7%, p < 0.001 for Gag LAI/ZM96). The study’s main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non–vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. Conclusions In this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy., Zoe Moodie and co-workers study immunological responses with DNA priming in trials of a candidate HIV vaccine., Author summary Why was this study done? HIV remains a major global health problem, especially in sub-Saharan Africa. Developing an efficacious HIV vaccine for subtype C infections, which predominate in southern Africa, is a high priority. Comparing immune responses after DNA plasmid versus viral vector priming in 2 similar subtype C HIV vaccine regimens could help inform the choice of priming strategy to use moving forward. DNA plasmid vaccines are cost-effective, easy to manufacture, and tolerable. What did the researchers do and find? We compared antibody and cellular immune responses to two phase I/II HIV-1 vaccines that differed in their priming mechanism (canarypox virus [ALVAC] vector versus DNA) but were matched in their protein boost and adjuvant. Specifically, we measured T-cell and binding and neutralizing antibody (nAb) responses to the vaccine-matched antigens from the HIV Vaccine Trials Network (HVTN) 100 and HVTN 111 trials. The vaccine regimens with DNA plasmid priming in general stimulated higher binding antibody (bAb) response magnitudes to the variable 1 and 2 (V1V2) correlates of decreased risk in RV144 and higher neutralizing responses to tier 1 viruses than the vaccine regimen with ALVAC priming. Both regimens stimulated high binding and neutralizing response rates, while DNA plasmid priming with MF59 adjuvanted protein boost induced significantly higher CD4+ T-cell response rates than ALVAC priming with MF59 adjuvanted protein boost. What do these findings mean? Our results suggest that DNA plasmid is a superior priming method for stimulating vaccine-matched humoral and cellular responses for HIV vaccine trials using this prime/boost approach. Additional investigations are warranted to optimize DNA plasmid delivery methods, such as electroporation for priming of DNA–protein combinations.

Published
2019

12. Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein

Author

Mina C, Hosseinipour, Craig, Innes, Sarita, Naidoo, Philipp, Mann, Julia, Hutter, Gita, Ramjee, Modulakgotla, Sebe, Lucas, Maganga, Michael E, Herce, Allan C, deCamp, Kyle, Marshall, One, Dintwe, Erica, Andersen-Nissen, Georgia D, Tomaras, Nonhlanhla, Mkhize, Lynn, Morris, Ryan, Jensen, Maurine D, Miner, Giuseppe, Pantaleo, Song, Ding, Olivier, Van Der Meeren, Susan W, Barnett, M Juliana, McElrath, Lawrence, Corey, James G, Kublin, and Daryl, Morris

Subjects
0301 basic medicine, Microbiology (medical), Adult, Squalene, HIV vaccine, MF59, C-DNA, Immunization, Secondary, Polysorbates, Zambia, HIV Infections, HIV Antibodies, Tanzania, 03 medical and health sciences, South Africa, 0302 clinical medicine, Immunogenicity, Vaccine, Medicine, Humans, 030212 general & internal medicine, Articles and Commentaries, AIDS Vaccines, business.industry, Immunogenicity, Biojector, HIV envelope protein, DNA, Virology, Clinical trial, Vaccination, Regimen, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00290, DNA prime/protein boost, HIV-1, subtype C, business
Abstract

Background The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. Methods In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1–uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. Results All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). Conclusions Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. Clinical Trials Registration South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27–0715–4917) and ClinicalTrials.gov (NCT02997969)., DNA and protein coadministration was associated with increased human immunodeficiency virus (HIV) type 1 V1/V2 antibody response. Biojector DNA administration elicited significantly greater CD4+ T-cell responses to HIV envelope protein than needle/syringe in the prime/boost but not the coadministration regimen.

Published
2019

13. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19)

Author

Mo Weijtens, Lauren Peter, Glenda Gray, Katleen Callewaert, Erica N. Borducchi, David C. Montefiori, Thomas B. Campbell, Frank Tomaka, Kathy Mngadi, Fatima Laher, Joseph P. Nkolola, David Jetton, Jenny Hendriks, Roland Zahn, Frances Priddy, Edith Swann, Juliet Mpendo, Sorachai Nitayapan, Karin Feddes-de Boer, Wenjun Li, Stephan Bart, Erica Lazarus, Abishek Chandrashekar, Jennifer Johnson, Frank Wegmann, Steven Nijs, Lindsey R. Baden, Merlin L. Robb, Nigel Garrett, Ludo Lavreys, Galit Alter, Dan H. Barouch, Etienne Karita, Hanneke Schuitemaker, Daniel J. Stieh, Georgia D. Tomaras, Nicole Frahm, M. Juliana McElrath, Danielle van Manen, Zelda Euler, Gregg Lucksinger, Lorenz Scheppler, Hannah Kibuuka, Robert Feldman, Raphaele Roten, Maria G. Pau, Kathryn E. Stephenson, Caroline Borremans, Nelson L. Michael, Punnee Pitisuttithum, Jessica Vreugdenhil, Jeroen Tolboom, Jerald C. Sadoff, Kundai Chinyenze, Bette T. Korber, Julia Hutter, and Academic Medical Center

Subjects
Adult, Diarrhea, 0301 basic medicine, medicine.medical_specialty, Modified vaccinia Ankara, Adolescent, Genetic Vectors, Population, Placebo, Dizziness, Adenoviridae, law.invention, Young Adult, 03 medical and health sciences, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Animals, Humans, Aspartate Aminotransferases, education, Adverse effect, Fatigue, AIDS Vaccines, Immunity, Cellular, education.field_of_study, Dose-Response Relationship, Drug, business.industry, General Medicine, Middle Aged, Macaca mulatta, Healthy Volunteers, Abdominal Pain, Immunity, Humoral, Vaccination, Clinical trial, 030104 developmental biology, Tolerability, Back Pain, HIV-1, business
Abstract

Summary Background More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. We aimed to evaluate mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials. Methods We conducted a multicentre, randomised, double-blind, placebo-controlled phase 1/2a trial (APPROACH). Participants were recruited from 12 clinics in east Africa, South Africa, Thailand, and the USA. We included healthy, HIV-1-uninfected participants (aged 18–50 years) who were considered at low risk for HIV-1 infection. We randomly assigned participants to one of eight study groups, stratified by region. Participants and investigators were blinded to the treatment allocation throughout the study. We primed participants at weeks 0 and 12 with Ad26.Mos.HIV (5 × 10 10 viral particles per 0·5 mL) expressing mosaic HIV-1 envelope (Env)/Gag/Pol antigens and gave boosters at weeks 24 and 48 with Ad26.Mos.HIV or modified vaccinia Ankara (MVA; 10 8 plaque-forming units per 0·5 mL) vectors with or without high-dose (250 μg) or low-dose (50 μg) aluminium adjuvanted clade C Env gp140 protein. Those in the control group received 0·9% saline. All study interventions were administered intramuscularly. Primary endpoints were safety and tolerability of the vaccine regimens and Env-specific binding antibody responses at week 28. Safety and immunogenicity were also assessed at week 52. All participants who received at least one vaccine dose or placebo were included in the safety analysis; immunogenicity was analysed using the per-protocol population. We also did a parallel study in rhesus monkeys (NHP 13-19) to assess the immunogenicity and protective efficacy of these vaccine regimens against a series of six repetitive, heterologous, intrarectal challenges with a rhesus peripheral blood mononuclear cell-derived challenge stock of simian-human immunodeficiency virus (SHIV-SF162P3). The APPROACH trial is registered with ClinicalTrials.gov, number NCT02315703. Findings Between Feb 24, 2015, and Oct 16, 2015, we randomly assigned 393 participants to receive at least one dose of study vaccine or placebo in the APPROACH trial. All vaccine regimens demonstrated favourable safety and tolerability. The most commonly reported solicited local adverse event was mild-to-moderate pain at the injection site (varying from 69% to 88% between the different active groups vs 49% in the placebo group). Five (1%) of 393 participants reported at least one grade 3 adverse event considered related to the vaccines: abdominal pain and diarrhoea (in the same participant), increased aspartate aminotransferase, postural dizziness, back pain, and malaise. The mosaic Ad26/Ad26 plus high-dose gp140 boost vaccine was the most immunogenic in humans; it elicited Env-specific binding antibody responses (100%) and antibody-dependent cellular phagocytosis responses (80%) at week 52, and T-cell responses at week 50 (83%). We also randomly assigned 72 rhesus monkeys to receive one of five different vaccine regimens or placebo in the NHP 13-19 study. Ad26/Ad26 plus gp140 boost induced similar magnitude, durability, and phenotype of immune responses in rhesus monkeys as compared with humans and afforded 67% protection against acquisition of SHIV-SF162P3 infection (two-sided Fisher's exact test p=0·007). Env-specific ELISA and enzyme-linked immunospot assay responses were the principal immune correlates of protection against SHIV challenge in monkeys. Interpretation The mosaic Ad26/Ad26 plus gp140 HIV-1 vaccine induced comparable and robust immune responses in humans and rhesus monkeys, and it provided significant protection against repetitive heterologous SHIV challenges in rhesus monkeys. This vaccine concept is currently being evaluated in a phase 2b clinical efficacy study in sub-Saharan Africa (NCT03060629). Funding Janssen Vaccines & Prevention BV, National Institutes of Health, Ragon Institute of MGH, MIT and Harvard, Henry M Jackson Foundation for the Advancement of Military Medicine, US Department of Defense, and International AIDS Vaccine Initiative.

Published
2018

14. Impact of body mass index on immunogenicity of pandemic H1N1 vaccine in children and adults

Author

Nadine Rouphael, Robyn A. Livingston, Karen L. Kotloff, Douglas Swanson, Paul Spearman, Christopher J. Harrison, Mark Wolff, Ina Stephens, Emmanuel B. Walter, Hana M. El Sahly, David I. Bernstein, Mark J. Mulligan, Kenneth E. Schmader, Wilbur H. Chen, Robert W. Frenck, Mary Anne Jackson, Jack T. Stapleton, Heather Hill, Sharon E. Frey, Angela L. Myers, Julia Hutter, Lisa A. Jackson, Patricia L. Winokur, Wendy A. Keitel, Rebecca C. Brady, Robert B. Belshe, Anna Wald, Andi L. Shane, Rowena J. Dolor, Robert L. Atmar, Shital M. Patel, Flor M. Munoz, Kathryn M. Edwards, Edwin L. Anderson, S. Todd Callahan, Harry L. Keyserling, Irene Graham, Sara A. Healy, Jennifer A. Whitaker, Allison Ross Eckard, Jason G. Newland, Srilatha Edupuganti, Susan Wooten, W. Paul Glezen, Janet A. Englund, and Jeffrey Meier

Subjects
Adult, medicine.medical_specialty, Adolescent, Influenza vaccine, Body Mass Index, Young Adult, Major Articles and Brief Reports, Influenza A Virus, H1N1 Subtype, Internal medicine, Pandemic, Influenza, Human, Immunology and Allergy, Medicine, Humans, Risk factor, Child, Aged, Hemagglutination assay, business.industry, Immunogenicity, Antibody titer, virus diseases, Infant, Middle Aged, medicine.disease, Obesity, Infectious Diseases, Influenza Vaccines, Child, Preschool, Immunology, business, Body mass index
Abstract

Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses.

Published
2014

15. Naturally acquired and conjugate vaccine-induced antibody to Haemophilus influenzae type b (Hib) polysaccharide in Malian children: serological assessment of the Hib immunization program in Mali

Author

Myron M. Levine, Marcela F. Pasetti, Milagritos D. Tapia, Doh Sanogo, Samba O. Sow, and Julia Hutter

Subjects
Male, Haemophilus Infections, Mali, complex mixtures, Serology, Conjugate vaccine, Polysaccharides, Virology, Medicine, Humans, Bacterial Capsules, Immunization Schedule, Haemophilus Vaccines, Vaccines, Conjugate, biology, business.industry, Transmission (medicine), Immunization Programs, Antibody titer, Haemophilus influenzae type b, Infant, Articles, Antibodies, Bacterial, Titer, Infectious Diseases, Carriage, Immunization, Immunology, biology.protein, bacteria, Parasitology, Female, Antibody, business
Abstract

Haemophilus influenzae type b (Hib) conjugate vaccine for infants (6, 10, and 14 weeks of age) was introduced into the Malian Expanded Program on Immunization in July 2005, to diminish invasive Hib disease in young children. Antibodies to Hib capsular polysaccharide (PRP) were measured in infants and toddlers from an area already served by the Hib immunization program (Bamako) and in unimmunized children of the same age in a district (Kangaba) where Hib immunization had not yet begun. Among vaccinated Bamako children 6-23 months of age, 77-93% exhibited PRP titers ≥ 1.0 μg/mL, indicating long-term protection, versus only 10-23% of Kangaba children of that age. High PRP antibody titers in immunized children persisted through 2 years of age. Moreover, ∼50% of Bamako children exhibited anti-PRP titers ≥ 5.0 μg/mL; a level that impedes Hib upper respiratory carriage, and may thereby diminish the Hib transmission to the unimmunized susceptible population (i.e., providing indirect protection).

Published
2012

18. Role of the C-type lectin receptors MCL and DCIR in experimental colitis.

Author

Julia Hütter, Magdalena Eriksson, Timo Johannssen, Robert Klopfleisch, Dorthe von Smolinski, Achim D Gruber, Peter H Seeberger, and Bernd Lepenies

Subjects
Medicine, Science
Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Though its exact etiology is still unclear, it is proposed that an imbalance in the intestinal homeostasis leads to a disturbed interaction between commensal microbiota and the mucosal immune system. Previous studies have shown that both innate and adaptive immunity are involved in an overwhelming colon inflammation, and thus contribute to the pathogenesis of IBD. In innate immunity, several pattern recognition receptors such as Toll-like receptors, NOD-like receptors or C-type lectin receptors (CLRs) are involved in IBD pathogenesis. Myeloid CLRs are mainly expressed by antigen-presenting cells and bind to glycan structures present on self or foreign antigens. The Macrophage-restricted C-type lectin (MCL) and the Dendritic cell immunoreceptor (DCIR) are two poorly characterized members of the CLR family. In this study, we investigated the role of MCL and DCIR in the pathogenesis of murine colitis. Both CLRs bound to intestinal microbiota to a different extent. They modulated the production of pro-inflammatory cytokines by antigen-presenting cells upon stimulation with heat-killed microbiota and impacted subsequent T cell responses. To analyze whether MCL and DCIR contribute to the pathogenesis of IBD, the dextran sulfate sodium (DSS) murine colitis model was employed. MCL-/- as well as DCIR-/- mice exhibited only a slightly increased severity of disease compared to wild-type mice indicating a limited role for MCL and DCIR in the regulation of intestinal immunity.

Published
2014
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