Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial

Youyi Fong; Lauren Dang; Bo Zhang; Jonathan Fintzi; Shiyu Chen; Jing Wang; Nadine G Rouphael; Angela R Branche; David J Diemert; Ann R Falsey; Cecilia Losada; Lindsey R Baden; Sharon E Frey; Jennifer A Whitaker; Susan J Little; Satoshi Kamidani; Emmanuel B Walter; Richard M Novak; Richard Rupp; Lisa A Jackson; Chenchen Yu; Craig A Magaret; Cindy Molitor; Bhavesh Borate; Tara M Babu; Angelica C Kottkamp; Anne F Luetkemeyer; Lilly C Immergluck; Rachel M Presti; Martín Bäcker; Patricia L Winokur; Siham M Mahgoub; Paul A Goepfert; Dahlene N Fusco; Robert L Atmar; Christine M Posavad; Jinjian Mu; Mat Makowski; Mamodikoe K Makhene; Seema U Nayak; Paul C Roberts; Dean Follmann; Peter B Gilbert; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team

doi:10.1093/cid/ciae465

Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial

Clin Infect Dis. 2024 Sep 26:ciae465. doi: 10.1093/cid/ciae465. Online ahead of print.

Authors

Youyi Fong^{1

2

3}, Lauren Dang⁴, Bo Zhang¹, Jonathan Fintzi⁴, Shiyu Chen¹, Jing Wang⁵, Nadine G Rouphael⁶, Angela R Branche⁷, David J Diemert⁸, Ann R Falsey⁷, Cecilia Losada⁶, Lindsey R Baden⁹, Sharon E Frey¹⁰, Jennifer A Whitaker¹¹, Susan J Little¹², Satoshi Kamidani^{13

14}, Emmanuel B Walter¹⁵, Richard M Novak¹⁶, Richard Rupp¹⁷, Lisa A Jackson¹⁸, Chenchen Yu¹, Craig A Magaret¹, Cindy Molitor¹, Bhavesh Borate¹, Tara M Babu¹⁹, Angelica C Kottkamp²⁰, Anne F Luetkemeyer²¹, Lilly C Immergluck²², Rachel M Presti²³, Martín Bäcker²⁴, Patricia L Winokur²⁵, Siham M Mahgoub²⁶, Paul A Goepfert²⁷, Dahlene N Fusco²⁸, Robert L Atmar¹¹, Christine M Posavad^{29

30}, Jinjian Mu³¹, Mat Makowski³¹, Mamodikoe K Makhene³², Seema U Nayak³², Paul C Roberts³², Dean Follmann⁴, Peter B Gilbert^{1

2

3}; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team

Collaborators

Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team:
David J Diemert, Elissa Malkin, Jeffrey M Bethony, Aimee Desrosiers, Marc Siegel, Angela R Branche, Ann R Falsey, Edward Walsh, Patrick Kingsley, Michael Peasley, Nadine G Rouphael, Cecilia Losada, Daniel S Graciaa, Hady Samaha, Paulina A Rebolledo, Zanthia Wiley, Lindsey R Baden, Amy C Sherman, Stephen R Walsh, Alexandra Tong, Rebecca Rooks, Sharon E Frey, Getahun Abate, Zacharoula Oikonomopoulou, Daniel F Hoft, Irene Graham, Jennifer A Whitaker, Hana M El Sahly, Wendy A Keitel, C Mary Healy, Robert L Atmar, Susan J Little, Thomas Cs Martin, Nicole Carter, Steven Hendrickx, Evan J Anderson, Christina A Rostad, Satoshi Kamidani, Etza Peters, Emmanuel B Walter, Michael J Smith, M Anthony Moody, Kenneth E Schmader, Richard M Novak, Benjamin G Ladner, Andrea Wendrow, Jessica Herrick, Richard Rupp, Laura Porterfield, Lisa A Jackson, Maya Dunstan, Rebecca Lau, Barbara Carste, Tara M Babu, Anna Wald, Taylor Krause, Kirsten Hauge, Angelica C Kottkamp, Mark J Mulligan, Tamia Davis, Celia Engelson, Vijaya Soma, Anne F Luetkemeyer, Chloe Harris, Azquena Munoz Lopez, Lilly C Immergluck, Erica Johnson, Austin Chan, Rachel M Presti, Jane A O'Halloran, Ryley M Thompson, Martín Bäcker, Andrew B Fleming, Asif Noor, Patricia L Winokur, Jeffery Meier, Jack Stapleton, Siham M Mahgoub, Celia Maxwell, Sarah Shami, Paul A Goepfert, Dahlene N Fusco, Arnaud C Drouin, Florice K Numbi, Kirsten E Lyke, David S Stephens, Kathleen M Neuzil, Monica M Farley, Jeanne Marrazzo, Sidnee Paschal Young, Jeffery Lennox, Robert L Atmar, Linda McNeil, Elizabeth Brown, Christine M Posavad, Megan A Meagher, Julie McElrath, Mike Gale, Kuleni Abebe, Mat Makowski, Heather Hill, Jim Albert, Holly Baughman, Lisa McQuarrie, Kalyani Telu, Jinjian Mu, Lisa J McQuarrie, Teri C Lewis, Lisa A Giebeig, Theresa M Engel, Caleb J Griffith, Wendi L McDonald, Alissa E Burkey, Lisa B Hoopengardner, Jessica E Linton, Nikki L Gettinger, David C Montefiori, Amanda Eaton, Derek J Smith, Antonia Netzl, Samuel H Wilks, Sina Türeli, Mamodikoe Makhene, Mohamed Elsafy, Rhonda Pikaart-Tautges, Janice Arega, Binh Hoang, Dan Curtin, Hyung Koo, Elisa Sindall, Sonja Crandon, Marciela M DeGrace, Diane J Post, Seema U Nayak, Paul C Roberts, John H Beigel, Nadine G Rouphael, Cecilia Losada, Daniel S Graciaa, Hady Samaha, Cassie Grimsley Ackerley, Kristen E Unterberger, Amy Anderson, Mary Atha, Kareem Bechnak, Sarah Bechnak, Mary Bower, Laura Clegg, Matthew Collins, Francine Dyer, Srilatha Edupuganti, Rebecca Fineman, Tigisty Girmay, Rebecca Gonzalez, Natalie Gray, Evan Gutter, Lisa Harewood, Chris Huerta, Brandi Johnson, Lauren Johnson, Colleen Kelley, Alexandra Koumanelis, Deborah Laryea, Hollie Macenczak, Nour Makkaoui, Michele McCullough, Tuong-Vy Ngo, Eileen Osinski, Julia Paine, Bernadine Panganiban, Rose Pope, Paulina Rebolledo, Susan Rogers, Erin Scherer, Veronica Smith, Andre Stringer, Jessica Traenkner, Dongli Wang, Alahna Watson, Stacey Wheeler, Jean Winter, Jianguo Xu, Lindsey R Baden, Amy C Sherman, Stephen R Walsh, Alexandra Tong, Rebecca Rooks, Jane A Kleinjan, Jon A Gothing, Andres A Avila Paz, Muneerah M Aleissa, Bethany Evans, August Heithoff, Natalie E Izaguirre, Hannah Jin, Urwah Kanwal, Austin Kim, Julia E Klopfer, Christina Montesano, John Almeida, Emily S Koleske, Hannah Levine, Nicholas P Morreale, Omolola Ometoruwa, Jun Bai Park Chang, Anna F Piermattei, Djenane M Pierre, Megan Powell, Kevin Zinchuk, Stephanie Pickford, Charles M Kelly Iii, Xiaofang Li, John Kupelian, Kimberly Dufresne, Xiaoguang Fan, Xi Zhang, Esther Arbona-Haddad, Jose Humberto Licona, Evan J Anderson, Christina A Rostad, Satoshi Kamidani, Etza Peters, Larry Anderson, Julia Bartol, Leisa Bower, Natsuko Campbell, Lisa Harewood, Hui-Mien Hsiao, Laila Hussaini, Inara Jooma, Gidget Kettle, Marcia Lewis, Wensheng Li, Cindy Lubbers, Lisa Macoy, Molly Morrison, Anna Siaw-Anim, Kathleen Stephens, Madeline Taylor, Ashley Tippett, Lauren Nolan, Anne F Luetkemeyer, Chloe Harris, Azquena Munoz Lopez, Daniel Berrner, Dennis Dentoni-Lasofsky, John Dwyer, Suzanne Hendler, Elvira Gomez, WeyLing Phuah, Jaime Velasco, Veronica Viar, David J Diemert, Elissa Malkin, Jeffrey M Bethony, Aimee Desrosiers, Marc Siegel, Nikita Schroll-McLaughlin, Jonathan Manning, Jane Ryu, Hanna-Grace Rabanes, Khadija Khan, Laura Vasquez, Caroline Thoreson, Larissa Scholte, Rafaela Thur, Peyton St John, Dorinne Mettle-Amuah, Patricia L Winokur, Jeffery Meier, Jack Stapleton, Laura Stulken, Theresa Hegmann, Deb Pfab, Elizabeth Morgan, Susan Herman, Angel Peguero, Michelle Rodenburg, Alfred J Carr, Delilah Johnson, Rachel M Presti, Jane A O'Halloran, Michael Klebert, Ryley M Thompson, Alem Haile, Kim Gray, Chapelle Ayres, Delaney Carani, Michael Royal, John Tran, Laura Blair, Anita Afghanzada, Natalie Schodl, Angelica C Kottkamp, Tamia Davis, Celia Engelson, Vijaya Soma, Abdulwahab Abdulai, Ashanay Allen, Natella Aronova, Philip Aziz, Emily Beato, Samuel Bliss, Jacqueline Callahan, Ellie Carmody, Amanda Dontino, Aimee Edwin, Shelby Goins, Sarah Haiken, Ramin Herati, Abdonnie Holder, Janice Hong, Trishala Karmacharya, Manpreet Kaur, Hye-Youn Kim, Alexander McMeeking, Mark Mulligan, Wai Ng, Edward Nirenberg, Irma Noriega, Samuel Nweke, Lalitha Parameswaran, Levonne Phillip, Stephanie Rettig, Marie Samanovic-Golden, Madalyn Saporito, Pamela Suman, Meron Tasissa, Michael Tuen, Julia Wagner, James Wilson, Doris Wong, Grace Yip, Samantha Yip, Heekoung Youn, Lisa Zhao, Angela R Branche, Ann R Falsey, Edward E Walsh, Patrick Kingsley, Arthur Zemanek, Katherine Elena, Spencer Obrecht, Ian Shannon, Amy Kaychalo, Erin Nowicki, Sharon Moorehead, Kari Steinmetz, Doreen Francis, Tanya Smith, William Hamilton, Jeanne Holden-Wiltse, Christopher Lane, Michael Peasley, Samuel Diehl, Kyle Richards, Stephen Bean, Nicole Dornbush, Carol Cole, Sharon E Frey, Getahun Abate, Zacharoula Oikonomopoulou, Daniel F Hoft, Irene Graham, Azra Blazevic, Tamara Blevins, Kathleen Chirco, Sabrina M DiPiazza, Stanley Doublin, Heather Hoertel Douds, Carol G Duane, Eric Eggemeyer, Linda M Eggemeyer-Sharpe, Lauren Nicole Foreman, Sarah Louise George, Geoffrey J Gorse, Michelle Harris, Helay Hassas, Rong Hou, Ryan Clark Kerr, Kate Elizabeth Liefer, Melissa J Loyet, Lainey Mejia-Jauregui, Keith Meyer, Tracy Renee Montauk, Karla J Mosby, Amanda Nethington, Huan Ning, Nicole Purcell, Joan M Siegner, Janice M Tennant, Mei Xia, Kiana Wilder, Yinyi Yu, Cassandra Nicole Zehenny, Richard Rupp, Laura Porterfield, Amber Stanford, Robert Cox, Kristin Pollock, Diane Barrett, Gerrianne Casey, Amy McMahan, Cori Burkett, Essie Cox, Martín Bäcker, Sarah J Pastolero, Kimberly Byrnes, Andrew B Fleming, Asif Noor, Sigridh A Muñoz-Gómez, Steven E Carsons, Sajumon K Joseph, Sophie Danziger, Monica Benitez, Maung Aung, Louis Ragolia, Alicia Vasile, April Correll, Christopher Hall, Thomas Palaia, Miloni H Thakker, Lavern Harvey, Lisa Zhao, Diana Badillo, Richard M Novak, Benjamin G Ladner, Andrea Wendrow, Jesica Herrick, Alfredo J Mena Lora, Scott A Borgetti, Diana L Bahena, Regina Harden, Renyce Powell, David C M Chan, Rebeca F Gasari, Michael Pacini, Margarita M Villarreal, Rodrigo Reyes, Samuel M Rene, Shannon M Whitted, Habiba Sultana, Nanu Kunwar, Tasmin Sultana, Md R Amin, Mahmood Ghassemi, Nia O'Neal, Chasity Serrano, Charlie Peterson, Emmanuel B Walter, Michael J Smith, M Anthony Moody, Kenneth E Schmader, Susan Doyle, Lynn S Harrington, Lori Hendrickson, Amy O'Berry, Sherry Huber, Janet Wootton, Kelly Clark, Lani Banez, Stephanie Smith, Byron Hauser, Ally Odom, Emily Randolph, Krystina Yoder, Kathlene Chmielewski, Luis Ballon, Aubree Latorre, Breana Montgomery, Antony Tritz, Thad Gurley, Margaret Pendzich, Lisa A Jackson, Maya Dunstan, Rebecca Lau, Barbara Carste, Wesley A Andersen, Lee Barr, Cassandra Bryant, Joe Choe, Lynn Gross, Erika Kiniry, Bonnie Y Lam, De Vona Lang, Stella Lee, Paula J Lins, Amy Mohelnitzky, Marilyn Nguyen, Matthew Nguyen, Melissa Resendiz Rivas, Melissa Boothe Scheer, Janice Suyehira, Stacie Wellwood, Maryann K Woodford, Susan J Little, Thomas Cs Martin, Nicole Carter, Steven Hendrickx, Ajay Bharti, Alyssa Phillips, Aurora Verduzco Gonzalez, Cheryl Dullano, Chris Houston, Dawn Rosenblum, DeeDee Pacheco, DeLys Brooks, Fang Wan, Helene Le, J C Alcantar, Jill Blumenthal, Joseph Lencioni, Kory Hess, Letty Muttera, Marlene Arredondo, Megan Smyth, Megan Taylor, Melinda Stafford, Michelle Orsburn, Michelle Truong, Niamh Higgins, Nimish Patel, Rebecca Gonzalez, Vivian Maldonado, Lilly C Immergluck, Erica Johnson, Austin Chan, Fatima Ali, Sonja Jackson, Noor Mohamed, LaKesha Tables, Norberto Fas, Kay Woodson, Saadia Khizer, Jacquelyn Ali, Abdullah Warsama, Eric Gaines, Sierra Jordan Thompson, Cristina Wilson, Trisha Parker, Xiting Lin, LaTeshia Thomas Seaton, Derrick Wilson, Siham M Mahgoub, Celia Maxwell, Sarah Shami, Edward Bauer, Yuanxiu Chen, Megan Ware-Pressley, Debra Ordor, Linda Fletcher, Emmanuel Baidoo, David Jaspan, Adetokunbo Adedokun, Michelle Strobeck, Michael A Riga, Ashley Karen Bautista, Jennifer A Whitaker, Hana M El Sahly, Wendy A Keitel, C Mary Healy, Robert L Atmar, Pedro A Piedra, Jesus Banay, Kathy Bosworth, Janet Brown, Kayla Burrell, Jeremy Castro, Tykel Eddy, Marcena Eubanks, Cathy Faw, Rachel Froebe, Alix Halter, Janey John, Chanei Henry, Vanessa Martinez, Carol Mundell, Brandie Phillips, Alicia Prevost-Barthe, Connie Rangel, Yolanda Rayford, Yvette Rugeley, Maria Shlyapobersky, Tina Sierra, Elizabeth Silguero, Lisreina Toro, Dawn Turner, Chianti Wade-Bowers, Jessica Woods, Robert L Atmar, Tara M Babu, Anna Wald, Taylor Krause, Kirsten Hauge, Jina Taub, Dana Varon, Britt Murphy, Morissa Pertik, T Nui Pholsena, Alyssa Braun, Jessica Heimonen, Amy Link, Lindsey McClellan, Jessica Moreno, Chloe Wilkens, Matt Seymour, Lawrence Hemingway, Jean Mernaugh, Chris McClurkan, Kerry Laing, Meredith Potochnic, Joong Kim, Bao-Chao Vo, Paul A Goepfert, Jenna Weber, Savannah Spaulding, Heather Logan, Faye Heard, Foreamben Patel, Michelle Chambers, Dahlene N Fusco, Arnaud C Drouin, Florice K Numbi, Hamada F Rady, Crystal A Ward, Quinn M Powers, William E Casey, Brian P Logarbo, Shae P Williams, Emily Callegari, David S Stephens, Kathleen M Neuzil, Monica M Farley, Jeanne Marrazzo, Sidnee Paschal Young, Jeffery Lennox, Robert L Atmar, Linda McNeil, Christine M Posavad, Megan A Meagher, Michael Stirewalt, John Hural, Weston Lawler, Lexi Tanser, Julie McElrath, Mike Gale, Elizabeth Brown, Kirsten E Lyke, Kuleni Abebe, Mat Makowski, Heather Hill, Jim Albert, Holly Baughman, Lisa McQuarrie, Kalyani Telu, Jinjian Mu, Lisa J McQuarrie, Teri C Lewis, Lisa A Giebeig, Theresa M Engel, Caleb J Griffith, Wendi L McDonald, Alissa E Burkey, Lisa B Hoopengardner, Jessica E Linton, Nikki L Gettinger, Aroussiak Bowen, Beth R Baseler, Vanessa S Eccard-Koons, Charles W R Hofsommer, Thomas C Sova, Gary A Krauss, David C Montefiori, Amanda Eaton, Francesca Suman, Derek J Smith, Antonia Netzl, Samuel H Wilks, Sina Türeli, Ana Mosterín Höpping, Samuel Turner, Sarah James, Poppy Roth, Marina Lee, Mamodikoe Makhene, Mohamed Elsafy, Rhonda Pikaart-Tautges, Janice Arega, Dan Curtin, Hyung Koo, Elisa Sindall, Aya Nakamura, Audria Crowder, Guinevere Chun, Frank Kenny, Seemi Patel, Sonia Gales, Ahsen Khan, Walla Dempsey, Robert Jurao, Sonja Crandon, Seema U Nayak, Marciela M DeGrace, Diane J Post, Paul C Roberts, John H Beigel

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
² Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
³ Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington, USA.
⁴ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁵ Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁶ Hope Clinic, Emory University, Decatur, Georgia, USA.
⁷ Vaccine and Treatment Evaluation Unit, University of Rochester, Rochester, New York, USA.
⁸ George Washington Vaccine Research Unit, George Washington University, Washington, District of Columbia, USA.
⁹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Center for Vaccine Development, Saint Louis University, Missouri, USA.
¹¹ Department of Molecular Virology and Microbiology and Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
¹² Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
¹³ Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Georgia, USA.
¹⁴ Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
¹⁵ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁶ Project WISH, University of Illinois at Chicago, Chicago, Illinois, USA.
¹⁷ Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
¹⁸ Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
¹⁹ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
²⁰ Vaccine and Treatment Evaluation Unit, Manhattan Research Clinic, New York University Grossman School of Medicine, New York, New York, USA.
²¹ Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, USA.
²² Clinical Research Center, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA.
²³ Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
²⁴ Vaccine and Treatment Evaluation Unit, Long Island Research Clinic, New York University, Long Island School of Medicine, Mineola, New York, USA.
²⁵ Department of Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA.
²⁶ Howard University College of Medicine, Howard University Hospital, Washington, District of Columbia, USA.
²⁷ Department of Medicine, University of Alabama at Birmingham, Alabama, USA.
²⁸ Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
²⁹ Infectious Diseases Clinical Research Consortium (IDCRC) Laboratory Operations Unit, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
³⁰ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
³¹ The Emmes Company, LLC, Rockville, Maryland, USA.
³² Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

PMID: 39325506
DOI: 10.1093/cid/ciae465

Abstract

For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

Keywords: COVID-19 booster; Omicron; correlate of risk; exposure-proximal titer; variant vaccine booster.

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Grants and funding

UM1 AI148685/AI/NIAID NIH HHS/United States