For Yue Tso1,2, Salum J Lidenge1,2,3,4, Lisa K Poppe1,2, Phoebe B Peña1,2, Sara R Privatt1,2, Sydney J Bennett1,2, John R Ngowi3, Julius Mwaiselage3,4, Michael Belshan1,5, Jacob A Siedlik6, Morgan A Raine5, Juan B Ochoa7, Julia Garcia-Diaz8, Bobby Nossaman8, Lyndsey Buckner8, W Mark Roberts8, Matthew J Dean9, Augusto C Ochoa9,10, John T West1,11, Charles Wood1,2,11. 1. Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, United States of America. 2. School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United States of America. 3. Ocean Road Cancer Institute, Dar es Salaam, Tanzania. 4. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 5. Department of Medical Microbiology & Immunology, Creighton University, Omaha, NE, United States of America. 6. Department of Exercise Science and Pre-Health Professions, Creighton University, Omaha, NE, United States of America. 7. Department of Surgery, Ochsner Medical Center, New Orleans, LA, United States of America. 8. Department of Internal Medicine Ochsner Medical Center, New Orleans, LA, United States of America. 9. Louisiana State University Cancer Center, New Orleans, LA, United States of America. 10. Department of Pediatrics LSU Health, New Orleans, LA, United States of America. 11. Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, United States of America.
Abstract
BACKGROUND: Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. METHODS: Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay. RESULTS: SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2. CONCLUSION: Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.
BACKGROUND: Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. METHODS:Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2spike pseudotyped virus. ADCC activity was assessed with a calcein release assay. RESULTS:SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2spike glycoprotein, including two individuals without nAb against SARS-CoV-2. CONCLUSION: Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.
Authors: Dieter Mielke; Sherry Stanfield-Oakley; Shalini Jha; Taylor Keyes; Adam Zalaquett; Brooke Dunn; Nicole Rodgers; Thomas Oguin; Greg D Sempowski; Raquel A Binder; Gregory C Gray; Shelly Karuna; Lawrence Corey; John Hural; Georgia D Tomaras; Justin Pollara; Guido Ferrari Journal: Cytometry A Date: 2022-04-01 Impact factor: 4.714
Authors: Marciela M DeGrace; Elodie Ghedin; Matthew B Frieman; Florian Krammer; Alba Grifoni; Arghavan Alisoltani; Galit Alter; Rama R Amara; Ralph S Baric; Dan H Barouch; Jesse D Bloom; Louis-Marie Bloyet; Gaston Bonenfant; Adrianus C M Boon; Eli A Boritz; Debbie L Bratt; Traci L Bricker; Liliana Brown; William J Buchser; Juan Manuel Carreño; Liel Cohen-Lavi; Tamarand L Darling; Meredith E Davis-Gardner; Bethany L Dearlove; Han Di; Meike Dittmann; Nicole A Doria-Rose; Daniel C Douek; Christian Drosten; Venkata-Viswanadh Edara; Ali Ellebedy; Thomas P Fabrizio; Guido Ferrari; Will M Fischer; William C Florence; Ron A M Fouchier; John Franks; Adolfo García-Sastre; Adam Godzik; Ana Silvia Gonzalez-Reiche; Aubree Gordon; Bart L Haagmans; Peter J Halfmann; David D Ho; Michael R Holbrook; Yaoxing Huang; Sarah L James; Lukasz Jaroszewski; Trushar Jeevan; Robert M Johnson; Terry C Jones; Astha Joshi; Yoshihiro Kawaoka; Lisa Kercher; Marion P G Koopmans; Bette Korber; Eilay Koren; Richard A Koup; Eric B LeGresley; Jacob E Lemieux; Mariel J Liebeskind; Zhuoming Liu; Brandi Livingston; James P Logue; Yang Luo; Adrian B McDermott; Margaret J McElrath; Victoria A Meliopoulos; Vineet D Menachery; David C Montefiori; Barbara Mühlemann; Vincent J Munster; Jenny E Munt; Manoj S Nair; Antonia Netzl; Anna M Niewiadomska; Sijy O'Dell; Andrew Pekosz; Stanley Perlman; Marjorie C Pontelli; Barry Rockx; Morgane Rolland; Paul W Rothlauf; Sinai Sacharen; Richard H Scheuermann; Stephen D Schmidt; Michael Schotsaert; Stacey Schultz-Cherry; Robert A Seder; Mayya Sedova; Alessandro Sette; Reed S Shabman; Xiaoying Shen; Pei-Yong Shi; Maulik Shukla; Viviana Simon; Spencer Stumpf; Nancy J Sullivan; Larissa B Thackray; James Theiler; Paul G Thomas; Sanja Trifkovic; Sina Türeli; Samuel A Turner; Maria A Vakaki; Harm van Bakel; Laura A VanBlargan; Leah R Vincent; Zachary S Wallace; Li Wang; Maple Wang; Pengfei Wang; Wei Wang; Scott C Weaver; Richard J Webby; Carol D Weiss; David E Wentworth; Stuart M Weston; Sean P J Whelan; Bradley M Whitener; Samuel H Wilks; Xuping Xie; Baoling Ying; Hyejin Yoon; Bin Zhou; Tomer Hertz; Derek J Smith; Michael S Diamond; Diane J Post; Mehul S Suthar Journal: Nature Date: 2022-03-31 Impact factor: 69.504